Neonatal outcome after prolonged preterm rupture of the membranes Avi Rotschild, MD, Emily W. Ling, MD, Martin L. Puterman, PhD, and Duncan Farquharson, MD Vancouver, British Columbia, Canada Pulmonary hypoplasia was diagnosed in 14 of 88 infants (16%) delivered in 1983 to 1986 after rupture of the membranes of "27 days with onset before 29 weeks' gestation. Logistic regression analYSis applied to examine the relative importance of perinatal risk factors in the prediction of pulmonary hypoplasia showed that gestational age at onset of rupture of the membranes had a significant effect (p = 0.002) on the odds that pulmonary hypoplasia developed in the neonate, whereas the duration of rupture of the membranes (p = 0.11) and the degree of oligohydramnios (p = 0.65) did not. Postnatally, the presence of pulmonary hypoplasia was associated with the severity of skeletal compreSSion deformities (p < 0.0001). The development of skeletal compression deformities was associated with severe oligohydramnios (p = 0.05) and duration of rupture of the membranes (p = 0.02) but not gestational age at rupture of the membranes (p = 0.77). Gestational age at onset of rupture of the membranes being the best single predictor of pulmonary hypoplasia suggests that the stage of lung development at rupture of the membranes may be important. (AM J OBSTET GVNECOL 1990;162:46-52.)
Key words: Fetal membranes, prolonged and premature rupture of the membranes, pulmonary hypoplasia, oligohydramnios Prolonged and preterm rupture of the membranes (PROM) is associated with increased chance of infection in both the mother and the fetus, perinatal death as a result of prematurity, and fetal distress during labor because of cord compression. Extended latency periods after PROM are associated with the additional risks of pulmonary hypoplasia and skeletal compression deformities.'·2 Current management protocols for PROM adopt a conservative and expectant approach to allow fetal maturity unless evidence of maternal or fetal infection dictates delivery. With the trends toward observation and expectant management in PROM, the association of oligohydramnios and pulmonary hypoplasia becomes increasingly important. Because pulmonary hypoplasia is associated with a high neonatal mortality rate,'" prenatal detection of its occurrence and severity would be helpful in the clinical management of PROM. Clinical studies"; in the past decade have suggested the following as significant risk factors for pulmonary hypoplasia: (1) gestational age at onset of rupture of membranes (ROM) before 26 weeks' gestation; (2) duration of ROM of>7 days; and (3) severity of oligohydramnios. From the Departments of Pediatrics and Obstetrics, University of British Columbia, and the Biostatistical Consulting Service, Re· search Division, British Columbia's Children's Hospital. Received for publication March 21, 1989; revised June 20, 1989; accepted July 24, 1989. Reprint requests: Emily W. Ling, MD, Department of Pediatrics, British Columbia's Children Hospital, 4480 Oak St., Vancouver, British Columbza, Canada V6H 3V4. 6/1 /15537
46
Because of the differences in the patient populations and methods of data analysis in the various studies, it is difficult to derive definitive conclusions from the results.6 In this study, we reviewed 88 neonates who were born after prolonged rupture of the membranes of "27 days and onset of rupture before 29 weeks' gestation with the objective of determining the relative importance of the individual risk factors in the prediction of pulmonary hypoplasia and severe skeletal deformities. Material and methods Study population. The population consisted of 88 infants admitted to the Neonatal Intensive Care Unit of British Columbia's Children's Hospital from 1983 to 1986 who were born after ROM of "27 days and in whom ROM occurred before 29 weeks' gestation. They were evaluated retrospectively by maternal and infant chart review. The diagnosis of ROM was confirmed as per usual practice by sterile speculum examination with pooled fluid, ferning, and alkaline pH determination. Infants with major congenital anomalies were excluded. All infants had normal kidneys. Of these 88 infants, 81 were inborn infants from the adjoining Grace Maternity Hospital and 7 were outborn infants transferred to the unit soon after birth. The quantity of amniotic fluid was estimated by fetal ultrasonographic examinations in the inborn and by ultrasonographic reports in most of the outborn cases. The last ultrasonographic examination was used , which was usually within 1 week before delivery. In 69/81 inborn infants, the decrease in amniotic fluid volume
Neonatal outcome in prolonged PROM
Volume 162 Number 1
47
Table I. Clinical profile of infants born after ROM of 2=.7 days that occurred before 29 weeks' gestation No pulmonary hypoplasia (n = 74)
Gestational age at birth (wk)* Birth weight (gm)* Gestational age at ROM (wk)* ROM (days)*
28.2 1191 25.1 22.4
Oligohydramnios Severe Moderate Deformities Severe Moderate Pneumothoraces Persistent pulmonary hypertension of the newborn Maternal amnionitis Neonatal infection Small for gestational age Died
± ± ± ±
2.16 362 2.68 18.5
(24-34) (640-2280) (15-28) (7-126)
Pulmonary hypoplasia (n = 14) 26.2 903 20.9 38.4
± 2.14 (24-31) ± 278 (580-1590) ± 3.17 (16-26) ± 20.9 (8-67)
26 (35%) 20 (27%)
7 (50%) 5 (36%)
0(0%) 9 (12%)
5 (36%) 4 (29%)
11 (15%) 8 (11%)
6 (43%)
35 (47%) 4 (5%) 6 (8%) 8 (11 %)
8 (57%) 0(0%) 1 (7%) 10 (71%)
9 (64%)
*Values are mean ± SD (range).
was semiquantitatively estimated by measurement of the depth of the largest fluid pocket. 7 The degree of oligohydramnios was graded as severe, moderate, or mild-normal if the largest pocket measured < 1.0 cm, 1.0 to 2.0 cm, or >2.0 cm. Qualitative assessment was available in another 10 infants with the use of visual criteria of obvious lack of fluid and evidence of fetal crowding (e.g., dolichocephaly). The diagnosis of pulmonary hypoplasia was made on the basis of clinical, radiologic, and pathologic evidence. Suggestive clinical signs' were small chest circumference, immediate onset of severe pulmonary insufficiency after birth requiring high ventilator pressures and unusual clinical course complicated by pneumothoraces, pulmonary interstitial emphysema, and persistent pulmonary hypertension. Radiologic criteria8 included small well-aerated lung fields with elevated diaphragms up to the seventh rib, downward sloping ribs with occasional dysplastic appearance, and a bellshaped chest. Pathologic diagnosis 9 was made on the basis of marked decreased lung weights of the expected for the gestational age with or without evidence of decreased radial alveolar counts. Information about skeletal deformities was obtained from the initial physical examination and they were graded as: mild, bruising with or without molding; moderate, compression abnormalities of limbs; and severe, Potter-like facies and limb abnormalities. Statistical methods. The relationship between the presence or absence of pulmonary hypoplasia and the presence or absence of severe skeletal compression deformities with gestational age at rupture (GAR), number of days of rupture (RDAYS) and extent of oligo-
hydramnios was investigated with multiple logistic regression and contingency table analysis. The logistic regression analysis was performed with gestational age at rupture and number of days of rupture both as continuous and categorical variables; only results from the former analysis are presented here. Logistic regression is based on representing the probability of pulmonary hypoplasia (or skeletal compression deformities) as a function of the values of gestational age at rupture, number of days of rupture, and oligohydramnios (represented by two categorical variables: OLIGOM, coded 1 for moderate and 0 otherwise, and aLI Gas, coded 1 for severe and 0 otherwise) as follows: Probability of pulmonary hypoplasia = 1/[1 + e-(~o + ~,GAR + ~2RDAYS + ~,OLlGOM +
~.OLlGOS)]
where e is the base of the natural logarithm system and 130' 13" 132, 133, and 13. are coefficients to be estimated. Results of these analyses are also presented in terms of odds ratio coefficients and associated 95% confidence intervals. These coefficients are the exponentiated regression coefficients and are useful for making comparative statements about the relative risks of pulmonary hypoplasia or skeletal compression deformities as functions of the individual or combined risk factors when the remaining factors are held fixed. They are multiplicative factors; values greater than one mean that increases in the value of the corresponding measurement increase the odds of the outcome, whereas values less than one correspond with decreases in the odds of the outcome. Inasmuch as the oligohydramnios variables aLIGaM and aLIGaS assume only the values of zero and one, these coefficients directly estimate
48
Rotschild et al.
January 1990 Am J Obstet Gynecol
30
25
Key words: Fetal membranes, prolonged and premature rupture of the membranes, pulmonary hypoplasia, oligohydramnios Prolonged and preterm rupture of the membranes (PROM) is associated with increased chance of infection in both the mother and the fetus, perinatal death as a result of prematurity, and fetal distress during labor because of cord compression. Extended latency periods after PROM are associated with the additional risks of pulmonary hypoplasia and skeletal compression deformities.'·2 Current management protocols for PROM adopt a conservative and expectant approach to allow fetal maturity unless evidence of maternal or fetal infection dictates delivery. With the trends toward observation and expectant management in PROM, the association of oligohydramnios and pulmonary hypoplasia becomes increasingly important. Because pulmonary hypoplasia is associated with a high neonatal mortality rate,'" prenatal detection of its occurrence and severity would be helpful in the clinical management of PROM. Clinical studies"; in the past decade have suggested the following as significant risk factors for pulmonary hypoplasia: (1) gestational age at onset of rupture of membranes (ROM) before 26 weeks' gestation; (2) duration of ROM of>7 days; and (3) severity of oligohydramnios. From the Departments of Pediatrics and Obstetrics, University of British Columbia, and the Biostatistical Consulting Service, Re· search Division, British Columbia's Children's Hospital. Received for publication March 21, 1989; revised June 20, 1989; accepted July 24, 1989. Reprint requests: Emily W. Ling, MD, Department of Pediatrics, British Columbia's Children Hospital, 4480 Oak St., Vancouver, British Columbza, Canada V6H 3V4. 6/1 /15537
46
Because of the differences in the patient populations and methods of data analysis in the various studies, it is difficult to derive definitive conclusions from the results.6 In this study, we reviewed 88 neonates who were born after prolonged rupture of the membranes of "27 days and onset of rupture before 29 weeks' gestation with the objective of determining the relative importance of the individual risk factors in the prediction of pulmonary hypoplasia and severe skeletal deformities. Material and methods Study population. The population consisted of 88 infants admitted to the Neonatal Intensive Care Unit of British Columbia's Children's Hospital from 1983 to 1986 who were born after ROM of "27 days and in whom ROM occurred before 29 weeks' gestation. They were evaluated retrospectively by maternal and infant chart review. The diagnosis of ROM was confirmed as per usual practice by sterile speculum examination with pooled fluid, ferning, and alkaline pH determination. Infants with major congenital anomalies were excluded. All infants had normal kidneys. Of these 88 infants, 81 were inborn infants from the adjoining Grace Maternity Hospital and 7 were outborn infants transferred to the unit soon after birth. The quantity of amniotic fluid was estimated by fetal ultrasonographic examinations in the inborn and by ultrasonographic reports in most of the outborn cases. The last ultrasonographic examination was used , which was usually within 1 week before delivery. In 69/81 inborn infants, the decrease in amniotic fluid volume
Neonatal outcome in prolonged PROM
Volume 162 Number 1
47
Table I. Clinical profile of infants born after ROM of 2=.7 days that occurred before 29 weeks' gestation No pulmonary hypoplasia (n = 74)
Gestational age at birth (wk)* Birth weight (gm)* Gestational age at ROM (wk)* ROM (days)*
28.2 1191 25.1 22.4
Oligohydramnios Severe Moderate Deformities Severe Moderate Pneumothoraces Persistent pulmonary hypertension of the newborn Maternal amnionitis Neonatal infection Small for gestational age Died
± ± ± ±
2.16 362 2.68 18.5
(24-34) (640-2280) (15-28) (7-126)
Pulmonary hypoplasia (n = 14) 26.2 903 20.9 38.4
± 2.14 (24-31) ± 278 (580-1590) ± 3.17 (16-26) ± 20.9 (8-67)
26 (35%) 20 (27%)
7 (50%) 5 (36%)
0(0%) 9 (12%)
5 (36%) 4 (29%)
11 (15%) 8 (11%)
6 (43%)
35 (47%) 4 (5%) 6 (8%) 8 (11 %)
8 (57%) 0(0%) 1 (7%) 10 (71%)
9 (64%)
*Values are mean ± SD (range).
was semiquantitatively estimated by measurement of the depth of the largest fluid pocket. 7 The degree of oligohydramnios was graded as severe, moderate, or mild-normal if the largest pocket measured < 1.0 cm, 1.0 to 2.0 cm, or >2.0 cm. Qualitative assessment was available in another 10 infants with the use of visual criteria of obvious lack of fluid and evidence of fetal crowding (e.g., dolichocephaly). The diagnosis of pulmonary hypoplasia was made on the basis of clinical, radiologic, and pathologic evidence. Suggestive clinical signs' were small chest circumference, immediate onset of severe pulmonary insufficiency after birth requiring high ventilator pressures and unusual clinical course complicated by pneumothoraces, pulmonary interstitial emphysema, and persistent pulmonary hypertension. Radiologic criteria8 included small well-aerated lung fields with elevated diaphragms up to the seventh rib, downward sloping ribs with occasional dysplastic appearance, and a bellshaped chest. Pathologic diagnosis 9 was made on the basis of marked decreased lung weights of the expected for the gestational age with or without evidence of decreased radial alveolar counts. Information about skeletal deformities was obtained from the initial physical examination and they were graded as: mild, bruising with or without molding; moderate, compression abnormalities of limbs; and severe, Potter-like facies and limb abnormalities. Statistical methods. The relationship between the presence or absence of pulmonary hypoplasia and the presence or absence of severe skeletal compression deformities with gestational age at rupture (GAR), number of days of rupture (RDAYS) and extent of oligo-
hydramnios was investigated with multiple logistic regression and contingency table analysis. The logistic regression analysis was performed with gestational age at rupture and number of days of rupture both as continuous and categorical variables; only results from the former analysis are presented here. Logistic regression is based on representing the probability of pulmonary hypoplasia (or skeletal compression deformities) as a function of the values of gestational age at rupture, number of days of rupture, and oligohydramnios (represented by two categorical variables: OLIGOM, coded 1 for moderate and 0 otherwise, and aLI Gas, coded 1 for severe and 0 otherwise) as follows: Probability of pulmonary hypoplasia = 1/[1 + e-(~o + ~,GAR + ~2RDAYS + ~,OLlGOM +
~.OLlGOS)]
where e is the base of the natural logarithm system and 130' 13" 132, 133, and 13. are coefficients to be estimated. Results of these analyses are also presented in terms of odds ratio coefficients and associated 95% confidence intervals. These coefficients are the exponentiated regression coefficients and are useful for making comparative statements about the relative risks of pulmonary hypoplasia or skeletal compression deformities as functions of the individual or combined risk factors when the remaining factors are held fixed. They are multiplicative factors; values greater than one mean that increases in the value of the corresponding measurement increase the odds of the outcome, whereas values less than one correspond with decreases in the odds of the outcome. Inasmuch as the oligohydramnios variables aLIGaM and aLIGaS assume only the values of zero and one, these coefficients directly estimate
48
Rotschild et al.
January 1990 Am J Obstet Gynecol
30
25
