Published online July 2, 2007
PEDIATRICS Vol. 120 No. 1 July 2007, pp. 84-89 (doi:10.1542/peds.2006-3680)
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ARTICLE

Hydrops Fetalis: A Retrospective Review of Cases Reported to a Large National Database and Identification of Risk Factors Associated With Death

Matthew E. Abrams, MDa,b, Keith S. Meredith, MDa,b, Paula Kinnard, RNa,b and Reese H. Clark, MDa

a Center for Research and Education, Pediatrix Medical Group, Sunrise, Florida
b Division of Neonatology, Phoenix Children's Hospital, Phoenix, Arizona


   ABSTRACT
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 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
OBJECTIVES. The objectives were (1) to identify the causes for hydrops fetalis neonates admitted for neonatal intensive care with the diagnosis of hydrops fetalis and (2) to identify the risk factors associated with death.

METHODS. A retrospective review of a large national data set was performed.

RESULTS. There were a total of 253651 discharges from 162 NICUs in the database; 598 patients were identified with a report of hydrops fetalis. The most common associated diagnoses were congenital heart problems (13.7%), abnormalities in heart rate (10.4%), twin-to-twin transfusion (9%), congenital anomalies (8.7%), chromosomal abnormalities (7.5%), congenital viral infections (6.7%), congenital anemia (5%), and congenital chylothorax (3.2%). Of those 598 neonates, 115 were transferred either to another hospital or to another service, 215 died before discharge, and 267 were discharged from the hospital. One patient did not have a discharge type listed and was not included in the outcome analysis. Mortality rates were highest among neonates with congenital anomalies (57.7%) and lowest among neonates with congenital chylothorax (5.9%). Factors that were associated independently with death in logistic regression analyses were younger gestational age, low 5-minute Apgar score, and need for high levels of support during the first day after birth (higher levels of inspired oxygen support and more often treated with high-frequency ventilation).

CONCLUSIONS. The risk of death among neonates with hydrops fetalis depends on the underlying diagnosis and is highest for those who are born more prematurely and those who are most ill immediately after birth. Information from this large study should prove useful for planning prospective studies and providing prenatal counseling to parents with an affected fetus.

Key Words: neonate • hydrops fetalis • death • lung hypoplasia

Hydrops fetalis continues to be a challenging entity in neonatal/perinatal medicine.1–7Hydrops, an end-stage process for a number of fetal diseases, results in tissue edema and effusions of multiple body cavities. The cause of hydrops fetalis is multifactorial, and the condition is often associated with high mortality rates, despite improvements in diagnosis and management.1,7,8

Because of early prenatal diagnosis and intervention, Rh disease is now a relatively uncommon cause of hydrops fetalis in neonates. Underlying mechanisms such as cardiac disease and arrhythmias are relatively straightforward to diagnose, whereas other disorders, such as lysosomal storage diseases, require careful investigation and specialty laboratories.9,10 There are many case reports in the literature attributing the underlying cause of hydrops to a number of disease entities.2–6,9,11–17 The goals of our study were to understand more completely the underlying etiologic causes of hydrops fetalis in a contemporary data set and to identify the risk factors associated with death.


   METHODS
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 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Pediatrix Medical Group health care professionals (doctors and nurse practitioners) providing care to neonates admitted for intensive care use a proprietary software system to generate clinical admission, discharge, and daily progress notes. These data are stored in a consolidated data set and then deidentified for quality assurance, research, and billing purposes. By using the deidentified data set, from which several other observations have been reported,18–20 we performed a retrospective case series review. Cases were identified by searching the diagnosis table in our database for the term hydrops fetalis. We included patients who were discharged between January 1, 1996, and March 1, 2005. Data on fluid accumulation in specific compartments were not reported consistently in the database; therefore, the diagnosis of hydrops fetalis did not always include a report of fluid in >1 body compartment. We did not capture data on neonates who died in the delivery room and who were not admitted for neonatal intensive care. Clinical data on these neonates were recorded during their hospitalizations. Pediatrix Medical Group provides intensive care services in 220 hospitals in 32 states and Puerto Rico (10 patients in our sample were from Puerto Rico). The data in the electronic database are used for medical chart documentation, billing, and quality improvement projects. Clinicians providing care to patients interact with the patients' data on a daily basis, to generate progress notes and billing information. Each day's notes are stored with diagnoses made. The local data are consolidated within the Pediatrix Medical Group data warehouse, deidentified, made compliant with Health Insurance Portability and Accountability Act of 1996 regulations, and configured into tables that can be joined and queried for statistical analyses. The Phoenix Children's Hospital institutional review board approved our research with the deidentified data set. Data analysis was performed only within the deidentified database.

Data on estimated gestational age represented the best estimates based on both obstetrical data and neonatal examination findings. Designation of race was based on the options contained in the database, which were white, black, Hispanic, Native American, and Asian. A z score was calculated for each patient ([weight of the patient – mean weight of healthy patients of the same gestational age]/SD for the normal population of the same gestational age). A high z score suggests that the patient's weight is greater than expected for a neonate of the given degree of gestational maturity. We used this term to estimate the degree of edema.

Our analytical approach to these data was descriptive in nature. Specific database tables within the data warehouse used for this analysis were "patients," "admissions," and "diagnoses." All reports of hydrops fetalis collected within the diagnosis table were reviewed. For each patient with a diagnosis of hydrops fetalis, all other associated diagnoses were reviewed for assignment of a potential etiologic cause. In addition, data on causes of death and problems at discharge were reviewed for determination of the "primary" etiologic factor associated with hydrops fetalis. Differences in the demographic characteristics of patients who died and those who were discharged home were analyzed by comparing the 2 population samples with univariate analyses. Continuous variables (estimated gestational age and birth weight) were evaluated with 2-tailed t tests. Categorical variables (eg, race and gender) were evaluated with 2-tailed {chi}2 tests. Nonparametric data were assessed with Kruskal-Wallis analysis of variance. After univariate analyses, we used multivariate logistic regression to calculate the adjusted odds ratio for death by comparing the neonates who died with those who were discharged home. Transferred patients were not included in this analysis. We incorporated in the logistic regression analysis the variables found in univariate analyses to be different for the treatment groups at a probability of <.1. Birth weight and gestational age were entered into the model as continuous variables. Cases with missing values for any of the independent variables were excluded from the analyses. All statistical analyses were performed by using JMP 5.0.1a (SAS Institute, Cary, NC).


   RESULTS
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 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Study Population
There were a total of 253651 discharges from 162 NICUs within the database during the study period (Table 1). We identified 598 patients (0.23%) with a report of hydrops fetalis in the diagnosis table. Of those 598 neonates, 115 (19%) were transferred either to another hospital or to another service, 215 (36%) died before discharge, and 267 (45%) were discharged from the hospital. One patient did not have a discharge type listed and is not included in the outcome analysis. Characteristics of the patients in each outcome group are shown in Table 1.


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  		TABLE 1 Demographic, Laboratory, and Treatment Data According to Outcome Group

 
Diseases Associated With Hydrops Fetalis
Of the 598 patients with a diagnosis of hydrops fetalis, a plausible cause could be found for 441 (73.7%) (Table 2). For 157 (26.3%), a cause could not be determined, and the degree of evaluation to determine a cause varied. Of those 157, 94 (60%) had reports of normal chromosomes, 92 (59%) had negative evaluation results for congenital viral infections, and 97 (61%) had reports of normal cardiac echocardiographic findings; 88 (56%) had reports of all 3. Forty-five (28.6%) of the 157 patients died within 3 days after birth, and 10 (6.4%) were transferred to another hospital at ≤3 days of age.


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  		TABLE 2 Causes and Outcomes

 
For the 441 patients with a cause, the most common diagnoses associated with hydrops fetalis were congenital heart disease (n = 82; 13.7%), cardiac arrhythmias (n = 62; 10.4%), twin-to-twin transfusion (n = 54; 9%), congenital anomalies (n = 52; 8.7%), chromosomal abnormalities (n = 45; 7.5%), congenital viral infections (n = 40; 6.7%), congenital anemia (n = 30; 5%), and congenital chylothorax (n = 19; 3.2%). Five of the patients with hydrops fetalis and a history of twin-to-twin transfusion had reports of fetal siblings who died in utero.

Risk Factors Associated With Death
Univariate analyses showed that, compared with neonates who were discharged from the hospital, neonates who died were smaller and more immature (but had higher z scores, which suggests more edema) (Table 1). In addition, neonates who died were sicker in the period immediately after delivery (lower Apgar scores, higher levels of inspired oxygen, and more often treated with high-frequency ventilation) and had lower platelet counts (Table 1). The mortality rate was highest among neonates with congenital anomalies (mortality rate: 57.7%) and lowest among neonates with congenital chylothorax (mortality rate: 5.9%). Factors that were associated independently with death in logistic regression analyses were younger gestational age, low 5-minute Apgar score, and need for high levels of support during the first day after birth (higher levels of inspired oxygen support and more often treated with high-frequency ventilation).


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Using a national data set, we have described the largest review of underlying causes of hydrops fetalis and identified risk factors for death. The most common diagnoses associated with hydrops fetalis were congenital heart problems, abnormalities in heart rate, twin-to-twin transfusion, congenital anomalies, chromosomal abnormalities, congenital viral infections, congenital anemia, and congenital chylothorax. Most previous studies had sample sizes of <100 patients, and only 2 of them attempted to identify risk factors associated with death.1,21–24 Similar to results reported by previous investigators,1,22 we noted that the prognosis for hydrops fetalis depended on the cause. In our data, the mortality rate was highest among neonates with congenital anomalies (mortality rate: 57.7%) and lowest among neonates with congenital chylothorax (mortality rate: 5.9%). Infants who died were more likely to be more premature and were sicker after birth (lower 5-minute Apgar scores, higher levels of inspired oxygen support, and more often treated with high-frequency ventilation during the first day after birth).

There are some limitations of a retrospective review of any data set that is accumulated as part of medical chart documentation. Retrospective studies are limited by incomplete data. Test or autopsy results that returned after infants died, were transferred, or were discharged might not have been entered into the database. In addition, early prenatal diagnosis may lead to early termination of the pregnancy. We did not obtain information regarding the timing and severity of prenatal presentation or interventions. Has et al25 reviewed 30 cases with hydrops fetalis diagnosed between 10 and 14 weeks of pregnancy. All pregnancies with nonimmune hydrops resulted in abortion, intrauterine fetal death, or termination of the pregnancy. Therefore, it is possible that more infants had a diagnosis than our analyses showed, and mortality rates among neonates with hydrops fetalis might be higher if we considered perinatal death.

We caution against using our data to make decisions regarding the timing of delivery. Immaturity (young gestational age at delivery) was an important risk factor associated with death. Delivering fetuses early to treat worsening hydrops may not improve survival rates. The diagnosis and management of hydrops fetalis continue to be challenges for perinatologists and neonatologists. Mortality rates are high, and treatment options are limited. The data on the outcomes for neonates who have hydrops fetalis and are admitted for neonatal intensive care should be helpful for planning prospective studies of specific interventions and for counseling parents.


   FOOTNOTES
 
Accepted Mar 1, 2007.

Address correspondence to Matthew E. Abrams, MD, Pediatrix Medical Group, Phoenix Children's Hospital, 1919 E Thomas, Building C, Phoenix, AZ 85016. E-mail: matthewabrams{at}cox.net

The authors have indicated they have no financial relationships relevant to this article to disclose.


   REFERENCES
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 REFERENCES
 

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PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics




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