Objective
Fetal lung maturity often is used as the sole criterion that late preterm infants are ready for postnatal life. We therefore tested the hypothesis that fetal lung maturity testing does not predict the absence of morbidity in late preterm infants.
Study Design
We performed a retrospective cohort study to examine 152 infants who were born in the late preterm (34 0/7 to 36 6/7 weeks) and early term (37 0/7 to 38 6/7 weeks) periods after mature fetal lung indices and compared them with 262 infants who were born at ≥39 weeks’ gestation and who were matched by mode of delivery.
Results
Despite documented fetal lung maturity, infants who were born at <39 weeks had significantly higher rates of neonatal morbidities compared with infants who were born at ≥39 weeks’ gestation. After adjustment for significant covariates, we found that infants who were born at <39 weeks’ gestation had an increased risk of composite adverse outcome (odds ratio, 3.66; 95% confidence interval, 1.48–9.09; P < .01).
Conclusion
Fetal lung maturity testing is insufficient to determine an infant’s readiness for postnatal life.
The American College of Obstetricians and Gynecologists (ACOG) currently recommends the delay of elective delivery until 39 weeks’ gestation and that fetal lung maturity test should be performed to avoid iatrogenic prematurity if the scheduled delivery is planned at <39 weeks’ gestation. Although ACOG notes that fetal lung maturity at <39 weeks’ gestation is not an indication for delivery, fetal lung maturity testing by amniocentesis for the purpose of delivery planning remains a common obstetric practice. In our institution, we calculated a rate of amniocentesis for fetal lung maturity of 15.5 per 1000 live births from the years 2005–2010 for such decision-making purposes.
Although some recent data exist for infants at 37-39 weeks’ gestation, no study has focused specifically on neonatal morbidity in late preterm (34 0/7 to 36 6/7 weeks) and early term (37 0/7 to 38 6/7 weeks) infants after documented mature lung indices in the mother’s amniotic fluid; these are the 2 groups in which fetal lung maturity is most commonly performed. Because documented fetal lung maturity sometimes is used to justify elective delivery at <39 weeks’ gestation and is equated with readiness for postnatal life, thereby qualifying an infant as “term,” we believed it important to focus on the spectrum of neonatal morbidity that was seen in this patient population. Although the morbidity that was seen in infants between 34 and 39 weeks’ gestation has been thought to be inconsequential and transient, more recent studies indicate that these infants are a particularly vulnerable population who comprise the greatest proportion of premature infants and may have graver long-term outcomes than previously suspected.
As such, the aim of our study was to examine the rate of neonatal morbidity in infants who were born from 34 0/7 to 38 6/7 weeks’ gestation after amniocentesis with documented fetal lung maturity, compared with a reference group of infants who were born from 39 0/7 to 40 6/7 weeks’ gestation. Because of continued physiologic and autonomic immaturity, we hypothesized that, despite documented fetal lung maturity, infants who are born at <39 weeks’ gestation would have significant neonatal morbidity.
Materials and Methods
We performed a retrospective cohort study, using a list of all mothers who had an amniocentesis for fetal lung maturity between January 1, 2005 and February 28, 2010, and subsequently delivered at Good Samaritan Hospital in Cincinnati, Ohio, the hospital with the largest delivery volume in the state. The study group included births to women between 34 0/7 and 38 6/7 weeks’ gestation after amniocentesis with documented fetal lung maturity. The reference group included births that occurred from gestational ages 39 0/7 to 40 6/7 weeks; the data were selected at random by the hospital’s medical records office for the years of our study period and were matched by rate of cesarean delivery, because this mode of delivery has been associated independently with neonatal morbidity. Pregnancies were dated according to the best obstetric estimate; dating from the last menstrual period and first antenatal ultrasound scans are used. The institutional review board approved the study.
Fetal lung maturity was affirmed when the mother’s amniotic fluid had 1 of the following indices that indicated maturity: assay with TDx-FLM II ≥55 mg surfactant/g albumin in the nondiabetic patient (≥70 mg surfactant/g albumin in the diabetic patient), presence of phosphatidylglycerol, or lamellar body count (LBC) at >29,000 per μL. Although the threshold levels for TDx-FLM II and phosphatidylglycerol assays are well-established as labeled here, the threshold level for LBC was determined according to the laboratory standards of the study institution. The fetal lung maturity panel at the study institution included all 3 tests; however, for a short time during the study period, the phosphatidylglycerol assay was not available. Apart from this period, all amniotic fluid samples were tested for fetal lung maturity with each of the 3 tests: TDx-FLM II assay, LBC, and phosphatidylglycerol assay.
Study exclusions were pregnancies that were complicated by congenital anomalies, chromosomal abnormalities, or multifetal gestation. Mothers who delivered outside the study institution were also excluded. The Figure shows the screening process that yielded the eventual study population of 152 infants who were born from 34 to 38 6/7 weeks’ gestation, after amniocentesis that documented lung maturity; the reference group of 262 infants was born between 39 to 40 6/7 weeks’ gestation.
The charts of all the women and their infants who met inclusion criteria were reviewed for the variables of interest. One study investigator abstracted data from all charts; a second investigator did a quality assurance review of 10% of the charts and found discrepancies in <5% of all data variables that were collected. The primary study outcome was a composite measurement of neonatal morbidity that included admission to neonatal intensive care, hypoglycemia that required intravenous infusion, treatment with antibiotics for presumed sepsis, gavage feeding, or treatment for hyperbilirubinemia with phototherapy. These neonatal outcomes were chosen to form the composite adverse outcome because they are common morbidities that are seen in the late preterm and early-term population and require a higher level of monitoring or follow-up evaluation than a healthy, uncomplicated newborn infant. Secondary outcomes included each of these individual morbidities, in addition to resuscitation required in the delivery room, hypoglycemia (documented glucose level, <45 mg/dL), sepsis evaluation (screening complete blood count and/or blood culture), need for central venous access, and length of stay. Respiratory outcome was evaluated through data that were collected about the need for ongoing respiratory support or oxygen and surfactant administration. At the study institution, mechanical ventilation and surfactant are considered when an infant has clinical signs of respiratory distress, with an elevated pCO 2 or FiO 2 of >40%. Admission to neonatal intensive care is required for infants at <34 weeks’ gestation; therefore, the infants in our study group would have otherwise been sent to the well-baby nursery if no other complications were present. Maternal demographic characteristics that were analyzed as possible confounders were mother’s age, history of premature delivery, history of cesarean delivery, and presence of labor before delivery. Pregnancy complications included hypertensive disease (chronic, gestational, or preeclampsia), diabetes mellitus (preexisting or gestational), prolonged rupture of membranes, oligohydramnios, preterm labor, or antenatal hospitalization.
Based on published reports, an estimated rate of composite adverse neonatal outcome of approximately 23% could be expected in the study group, which was calculated from a rate of 30% in births at 34 0/7 to 36 6/7 weeks’ gestation and 15.7% in births at 36 0/7 to 38 6/7 weeks’ gestation. Assuming a 5% rate of composite adverse neonatal outcome in the comparison group of births at 39 0/7 to 40 6/7 weeks’ gestation, a sample size of 68 subjects in each group would be required to detect the aforementioned difference in composite adverse neonatal outcome with 80% power and an alpha of 0.05. During the study period, we identified 152 patients who met inclusion criteria for the study group. We then randomly selected 119 subjects for the reference group. Because of significant differences in the rate of cesarean delivery between the 2 groups (67% in the study group and 28% in the comparison group), we increased the sample size of the reference group to match the rate of cesarean deliveries (67%) to the study group. These additional reference group subjects were also selected at random from births during the study period, which yielded a final sample size of 262 for the reference group, with births at 39 0/7 to 40 6/7 weeks’ gestation.
The data were analyzed with SAS software (version 9.2; SAS Institute, Inc, Cary, NC). Differences between categoric and continuous variables were tested with the χ 2 (or Fisher’s exact test, where necessary) and Kruskal-Wallis test, respectively. Multivariate logistic regression was used to estimate the odds of composite adverse neonatal outcome for infants who were born after amniocentesis with documented lung maturity and were adjusted for covariates with significant differences that were seen in univariate analyses. Backward selection yielded a final model of statistically influential and biologically plausible covariates. Covariates that were included in the final model were hypertensive disease, diabetes mellitus, birthweight of infant, use of antenatal steroids, history of cesarean delivery, and presence of labor before delivery. Comparisons with associated probability values < .05 and 95% confidence intervals (CIs) that were not inclusive of the null value of 1 were considered statistically significant differences.
Results
Of the 735 charts that were screened of women who had amniocenteses for fetal lung maturity testing during the study period ( Figure ), 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 ( Table 1 ). 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.
| Maternal characteristic | Mature amniocentesis at 34.0–38.6 wk of gestation (n = 152) | Reference group at ≥39.0 wk of gestation (n = 262) | P value |
|---|---|---|---|
| Maternal age, y a | 29.2 ± 6.3 | 27.8 ± 6.3 | .04 |
| History of premature infant, n (%) | 57 (37.5) | 20 (7.6) | < .01 |
| History of cesarean delivery, n (%) | 68 (44.7) | 70 (26.8) | < .01 |
| Cesarean delivery, n (%) | 103 (67.8) | 171 (65.3) | .60 |
| Hypertensive disease, n (%) | 33 (21.7) | 16 (6.1) | < .01 |
| Diabetes mellitus, n (%) | 40 (26.3) | 21 (8.0) | < .01 |
| Premature rupture of membranes, n (%) | 2 (1.3) | 0 | .13 |
| Preterm labor, n (%) | 22 (14.5) | 2 (0.8) | < .01 |
| Intrauterine growth restriction, n (%) | 9 (5.9) | 2 (0.8) | < .01 |
| Oligohydramnios, n (%) | 14 (9.2) | 13 (5.0) | .09 |
| Antenatal steroids, n (%) | 15 (10.1) | 0 | < .01 |
| Presence of labor before delivery, n (%) | 71 (46.7) | 184 (70.2) | < .01 |
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