Of the 735 charts that were screened of women who had amniocenteses for fetal lung maturity testing during the study period (), 152 women and infants met inclusion criteria and had documented fetal lung maturity by at least 1 of the 3 fetal lung maturity tests measured on the panel (TDx-FLM II, phosphatidylglycerol, or LBC). Fetal lung maturity was positive by TDx-FLM II (61.2%), by phosphatidylglycerol (45.7%), and by LBC (74.3%) of the time. Of the women with positive fetal lung maturity, 40% had only 1 mature fetal lung test; 39% had 2 mature indices, and 20% had 3 mature indices.
Women who delivered at <39 weeks’ gestation after an amniocentesis with mature fetal lung indices had a higher incidence of a previous premature infant and previous cesarean delivery, hypertensive disease and diabetes mellitus, preterm labor, and intrauterine growth restriction (). More women in the reference group (delivery at ≥39 weeks’ gestation) had the presence of labor before delivery. Of the women who did undergo labor, 78.9% of the women in the study group were induced, as compared with 45.1% of the women in the reference group (P < .01). Of note, 10.1% of the women (15 patients) in the study group also received antenatal steroids.
Comparison of maternal factors
Taking into consideration the important effect of gestational age on neonatal outcomes, we stratified our study group, all of whom were born after mature amniocentesis, into those born late preterm (34 0/7 to 36 6/7 weeks’ gestation) and early term (37 0/7 to 38 6/7 weeks’ gestation), according to the classification by Engle and Kominarek10
(). The rate of composite adverse neonatal outcome was significantly higher in both the late preterm and early-term infants who were born after mature amniocentesis, compared with the reference group. Rates of composite adverse outcome, hypoglycemia, treatment with intravenous fluids, gavage feeding, phototherapy, sepsis evaluation, neonatal intensive care admission, and oxygen supplementation were significantly different when compared among the 3 groups. We also compared the late preterm group and early-term group separately with the reference group who were born at >39 weeks’ gestation. Despite the assertion that infants who are born at >37 weeks’ gestation have little morbidity, we found significant increases in the incidence of composite adverse neonatal outcome, hypoglycemia, phototherapy, and need for oxygen supplementation in early-term infants compared with the reference group.
Comparison of neonatal factors by late preterm, early term, and term
We repeated analyses and compared the 2 groups for neonatal outcomes by changing the criteria by which fetal lung maturity was determined, using 1 fetal lung maturity test at a time (). When each test was used individually and when TDx-FLM II assay was used in combination with phosphatidylglycerol assay (after omission of LBC), significant differences in composite score, hypoglycemia, gavage feeding, sepsis evaluation, and neonatal intensive care admission remained.
Adverse neonatal outcomes by fetal lung maturity test
Because differences in the rates of maternal medical comorbidities, steroid administration, and previous cesarean delivery between the study and reference groups could influence neonatal outcome, we examined the effect of potential confounding by these factors in 2 ways. First, we removed women with medical comorbidities from the cohort and repeated our analysis comparing the association between adverse neonatal outcomes between the mature amniocentesis study group and the >39-week gestation reference group in women who were most likely to be low risk (remaining, 76 in the study group and 214 in the reference group). Mothers with the complications of hypertensive disorders, premature rupture of membranes, diabetes mellitus, growth restriction, and oligohydramnios were those considered to have medical comorbidities. These maternal or fetal conditions are recognized by ACOG to be possible indications for delivery at <39 weeks’ gestation11
and that these mothers may have infants who are predisposed to greater morbidity. In a similar fashion, to assess the potential influence of antenatal steroid administration on the relationship between mature amniocentesis and neonatal outcome, we removed the 15 mothers from the cohort who received steroids during their pregnancy and repeated the analysis. Finally, we performed a third subanalysis of only the mothers who had a history of cesarean delivery. In the study group, fetal lung maturity testing was ordered before their repeat cesarean delivery (remaining, 68 in the study group and 70 in the reference group). In these 3 separate subanalyses, despite removal of high-risk groups, we continued to find significant differences (P
< .05) in the incidence of the composite adverse neonatal outcome between the study and reference groups.
Second, we used multivariate regression analyses to account for potential confounding. Using multivariate modeling, we assessed the association between adverse neonatal outcome and mature amniocentesis while adjusting the risk estimate for these same influential factors as noted earlier: medical comorbidities, onset of labor before delivery, antenatal steroids, and cesarean delivery. With this approach, the risk of composite adverse neonatal outcome in women who delivered at <39 weeks’ gestation after an amniocentesis with mature fetal lung indices was 3.66-fold increased (95% CI, 1.48–9.09; P <.01), compared with deliveries at ≥39 weeks’ gestation, even after adjustment for important confounding factors that included hypertensive disease, diabetes mellitus, birthweight of infant, use of antenatal steroids, history of cesarean delivery, and presence of labor before delivery. When we analyzed the subgroup of infants (n = 71) after removal of mothers with medical comorbidities that included diabetes mellitus, hypertension, oligohydramnios, intrauterine growth restriction or premature rupture of membranes, or administration of antenatal corticosteroids, we continued to find 3.22-fold higher risk (95% CI, 1.14–9.07; P = .03) of adverse outcome in infants who were delivered at <39 weeks’ gestation after mature amniocentesis and after adjustment for onset of labor before delivery and history of cesarean delivery.
Furthermore, after stratifying the study group by gestational age, we found that the risk of adverse neonatal outcome was increased for both late preterm births (odds ratio, 3.56; 95% CI, 1.15–11.03; P = .03), and early-term births (odds ratio, 3.73; 95% CI, 1.38–10.06; P < .01), compared with those pregnancies that delivered at >39 weeks’ gestation, after adjustment for the same important confounding factors. Additionally, despite accounting for the same confounding factors, infants who were born at <39 weeks’ gestation, despite mature fetal lung indices, also had significantly higher risk of hypoglycemia, need for phototherapy, and oxygen supplementation ().
Risk of neonatal morbidity in infants with positive fetal lung maturity