Clinician to Clinician: Reaffirming the role of lung maturity testing in the at-risk pregnancy

Dr. Stiller is Chief, Section of Maternal Fetal Medicine, Department of Obstetrics and Gynecology,
Bridgeport Hospital, Yale New Haven Health System, Bridgeport, Connecticut.

Dr. Sharuk is Resident Physician, Department of Obstetrics and Gynecology,
Bridgeport Hospital, Yale New Haven Health System, Bridgeport, Connecticut.

Dr. Laifer is Chief, Section of Obstetrics, Department of Obstetrics and Gynecology, Bridgeport Hospital,
Yale New Haven Health System, Bridgeport, Connecticut.

The authors have no conflicts of interest to report with respect to the content of this article.

Obstetricians often find themselves in clinical situations in which they have to ask the question, “Is delivery indicated for the benefit of the mother and/or fetus, or can this pregnancy be safely continued?” Many clinical scenarios pose risks that can be difficult to predict, even when using our best judgment and tools. Although it is not perfect, antenatal fetal monitoring is one such tool that we use in everyday practice to assess fetal health.¹ It can help us to decide to deliver a preterm fetus if compromise is suspected, or reassure us that delivery can be safely delayed.

Amniocentesis for fetal lung maturity (FLM) assessment is another tool in our armamentarium that can help us decide which at-risk fetuses or mothers might be better delivered rather than subjected to continued expectant management. More specifically, if the risk of respiratory distress syndrome (RDS) is low (ie, FLM confirmed), delivery before fetal or maternal complications occurs becomes would be more likely. For example, risk of stillbirth and RDS is higher in patients with poorly controlled pregestational diabetes, making documentation of lung maturity an important management tool. Performing amniocentesis to assess FLM, however, has recently come under strong criticism.

Historical perspective

Published in 2013, American College of Obstetricians and Gynecologists (ACOG) Committee Opinion No 560, “Medically Indicated Late-Preterm and Early-Term Deliveries,” reviewed evidence about neonatal morbidities associated with the late preterm (34–36 6/7 weeks) and early-term (37–38 6/7 weeks) pregnancy.²

In addition to major neonatal morbidities (such as RDS, intraventricular hemorrhage, and necrotizing enterocolitis), minor morbidities (such as temperature instability, hyperbilirubinemia, feeding difficulties, and admission to newborn intensive care units) were also considered. The two important and useful purposes that the document served were discouraging elective delivery prior to 39 weeks because of increased neonatal morbidity in these late-preterm and early term deliveries, even when lung maturity was documented and providing guidance and recommendations as to when pregnancies might be delivered in a setting complicated by selected medical or fetal complications.

The authors suggested that “amniocentesis for the determination of lung maturity in well dated pregnancies generally should not be used to guide the time of delivery.”² However, we believe that the rationales cited were rather simplistic. If a patient needs to be delivered, then she should be delivered, regardless of fetal lung maturity. And if a patient doesn’t need to be delivered, then we should wait.

The ACOG authors listed a number of maternal and fetal complications and suggested gestational age intervals for delivery. For example, in women with placenta previa, delivery between 36 0/7 weeks and 37 6/7 weeks-a 14-day window-was suggested. In women with pregestational diabetes with vascular complications and those with chronic hypertension on medication, delivery between 37 0/7 weeks and 39 6/7 weeks-a 21-day window-was recommended. For poorly controlled pregestational diabetes, it was recommended that the timing of delivery be “individualized.”

How does an ob/gyn decide when in that wide 14- to 21-day window delivery should be performed? How do we manage patients with these conditions and offer consultation to referring doctors? Like the uncertainty of a Category II fetal heart rate monitor tracing, some conditions are not simply black or white. Of course, we can all agree that if there is clear maternal or fetal compromise, immediate delivery regardless of lung maturity is recommended. But there are various maternal and fetal complications that confer potential-but perhaps not immediate-risks to continuing the pregnancy.

For many years evaluation of FLM helped us decide when, during a possible 2– to 3-week interval, delivery could more safely be conducted. So how did amniocentesis lose favor in these situations? There was recognition that amniocentesis might be misused in justifying an early delivery in the absence of a strong medical indication. A series of studies shows, not surprisingly, that fetuses delivered at 34–37 weeks, even in the presence of documented lung maturity, have greater neonatal morbidity than those delivered at 39 weeks.^3,4

Those studies, however, did not address the risks to these fetuses of remaining undelivered, especially in the setting of coexisting maternal complications. Retrospectively comparing women who underwent amniocentesis at 34–36 weeks to women who were able to deliver at 39 weeks or greater was not a fair comparison. It just confirms what we already know: If the indication for delivery is purely elective and no harm will come if we wait until 39 weeks, it is, in fact, best to wait.

Another contributing factor was discontinuation in 2012 of the Abbott TDx FLM assay, a commercial rapid FLM test. Some centers are no longer able to process amniotic fluid because thin-layer chromatography for lecithin–sphingomyelin (L/S) ratios is not readily available at all institutions.

At Bridgeport Hospital, a community teaching hospital in Bridgeport, Connecticut, we have moved to lamellar body analysis and found it very helpful, using a value of >50,000 μL as representing lung maturity in the nondiabetic patient. We reserve L/S testing as a send-out for diabetic patients and those with borderline results. A recent meta-analysis confirms that its accuracy is similar to that of L/S ratio testing.⁵

Balancing benefits and risks

Despite the recent approach that ACOG has advocated, we maintain that there may be significant clinical benefit for evaluation of FLM.

In clinical practice, we cannot predict what will happen in a complicated pregnancy by waiting an additional 1–3 weeks. Take, for example, a woman with a previous classical cesarean delivery, in whom the potential exists for a catastrophic complication such as uterine rupture. In that case, one might not choose to delay delivery until 37 6/7 weeks, and that is acceptable under the new ACOG guidelines, especially if lung maturity is ensured. In a decision analysis study, Stotland et al used mathematic modeling and showed a trade-off of 22 cases of RDS to prevent 1 case of hypoxic ischemic encephalopathy after uterine rupture if delivery at 36 weeks was used.⁶

When trying to counsel a patient with several unknown risks (ie, risk to the fetus with immediate delivery, risk of possible fetal or maternal complications with delayed delivery), knowledge about lung maturity provides useful adjunctive information that is unique and relevant to the patient, and not just in the form of statistics. Our patients deserve the most accurate assessment of risks and benefits we can provide.

Another part of the equation in deciding the value of amniocentesis involves the overall risk of RDS during the late preterm/early preterm periods. Risk of RDS does decrease with increasing gestational age. One study showed that if FLM testing indicated maturity, the risk of RDS was 3%. However, if it indicated immaturity, the risk increased to 30%, depending upon gestational age.⁷

Lastly, for institutions with limited nursery capabilities, the information on lung maturity, although not perfect, may help in determining whether patients might safely be delivered at their primary hospital, rather than after transfer to distant sites.

We are not alone in these concerns. Towers et al, authors who come from four university centers, wrote a recent editorial in the American Journal of Obstetrics and Gynecology positing a similar argument about the value of amniocentesis for lung maturity determination in these at-risk patients.⁸

We don’t want to discount the potential risks associated with amniocentesis for FLM, which include rupture of membranes, initiation of labor, and infection. It is important to note that the greatest risk has been associated with diagnostic (genetic) amniocentesis in the second trimester, when risk of labor or rupture could result in loss of the pregnancy.

In a recent study on amniocentesis risks in the third trimester, the procedure was not associated with a statistically increased risk of urgent delivery or perinatal death.⁹ Nevertheless, amniocentesis for FLM should be considered only when it is technically feasible and safe, based on ultrasound evaluation of the position of the fetus, location of the placenta, and amniotic fluid volume.

The Executive Summary Guidelines from the NICHD workshop “Timing of Indicated Late Preterm and Early Term Births” state “it is critical that the totality of the clinical picture be taken into account when deciding the optimal timing of delivery.”¹⁰

We strongly believe that knowledge of FLM through amniocentesis, albeit not perfect, nor a guarantee that an infant will not suffer any neonatal morbidity, will help us to better plan deliveries of women with complicated pregnancies and who carry risk, should the pregnancy continue. 

References

1. American College of Obstetricians and Gynecologists. Antepartum fetal surveillance. ACOG Practice Bulletin no. 145. July 2014.

2. American College of Obstetricians and Gynecologists. ACOG Committee Opinion no. 560. Medically Indicated late-preterm and early-term deliveries. Obstet Gynecol. 2013;121:908–910.

3. Bates E, Rouse DJ , Mann ML, Chapman V, Carlo WA, Tita ATN. Neonatal outcomes after demonstrated fetal lung maturity before 39 weeks of gestation. Obstet Gynecol. 2010;116:1288–1295.

4. Kamath BD, Marcotte MP, DeFranco EA. Neonatal morbidity after documented fetal lung maturity in late preterm and early term infants. Am J Obstet Gynecol. 2012;207:222.e1–4.

5. Besnard AE, Wirjosoekarto SA, Broeze KA, Opmeer BC, Mol BW. Lecithin/sphingomyelin ratio and lamellar body count for fetal lung maturity: a meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2013 169:177–183.

6. Stotland N, Lipshitz L, Caughey A. Delivery strategies for women with a previous classical cesarean delivery: a decision analysis. Am J Obstet Gynecol. 2002;187:1203–1208.

7. Neerhof MG. Haney EI, Silver RK, Ashwood ER, Lee I-S, Piazze JJ. Lamellar body counts compared with traditional phospholipid analysis as an assay for evaluating fetal lung maturity. Obstet Gynecol. 2001;97;305–309.

8. Towers CV, Freeman RK, Nageotte MP, Garite TJ, Lewis DF, Quilligan EJ et al. The case for amniocentesis for fetal lung maturity in late-preterm and early-term gestations. Am J Obstet Gynecol. 2014; 210: 95–96.

9. Hodor JG, Poggi SH, Spong CY, et al. Risk of third-trimester amniocentesis: a case-control study. Am J Perinatol. 2006 Apr;23(3):177–180.

10. Spong CY, Mercer BM, D’Alton M, Kilpatrick S, Blackwell S, Saade G. Timing of indicated late-preterm and early-term birth. Obstet Gynecol. 2011;118:323–333.