Lung maturation in small for gestational age fetuses from pregnancies complicated by placental insufficiency or maternal hypertension

https://doi.org/10.1016/j.earlhumdev.2007.12.006Get rights and content

Abstract

Background

Clinical studies suggest that respiratory outcome of infants born preterm may be influenced by placental insufficiency and hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. If so, one could expect to see differences in lung maturation indices (lecithin/sphingomyelin (L/S) ratio and lamellar body count (LBC)) in the amniotic fluid. The present study investigates lung maturation indices of preterm small for gestational age (SGA) fetuses with or without abnormal Doppler ultrasound examination and with or without maternal hypertension/HELLP syndrome.

Study design

Retrospective cohort study of 76 neonates born in our center between 1997 and 2003 with gestational age (GA) < 34 weeks, birth weight < p10 for GA and available results from amniocentesis. All analyses were corrected for potential confounders.

Results

The L/S ratio was significantly higher in the abnormal Doppler group as compared to the normal Doppler group (p = 0.02). The L/S ratio was significantly lower in hypertensive pregnancies as compared to normotensive pregnancies (p = 0.02). Subdivision of the maternal hypertension group showed a significantly lower L/S ratio in the HELLP syndrome group as compared to the normotension group (p = 0.04).

Conclusion

The L/S ratio of SGA fetuses is significantly higher in cases with presumed placental insufficiency and significantly lower when pregnancies are complicated by HELLP syndrome. These observations are in line with the hypothesis that placental insufficiency accelerates lung maturation and with recent reports of poorer respiratory outcome in infants from mothers with HELLP syndrome.

Introduction

Low fetal weight for gestational age is an important cause of neonatal morbidity and mortality [1], [2], [3]. When fetal weight is below the 10th percentile for gestational age the fetus is designated as being small for gestational age (SGA). SGA may be caused by many factors including placental insufficiency which can be objectified by Doppler ultrasound examination [4]. It has been hypothesized that placental insufficiency may accelerate pulmonary maturation through chronic intrauterine stress [5]. However, to date no studies have been able to confirm this hypothesis [4], [6], [7], [8]. Contrary to expectation, two groups have reported a higher respiratory distress syndrome (RDS) incidence in infants with abnormal prenatal Doppler examination [6], [7]. Furthermore, recently we and others have shown that hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome [9] increases respiratory morbidity in preterm neonates [8], [10], indicating impaired pulmonary development.

If lung development is influenced by placental insufficiency and HELLP syndrome, one would expect to see differences in lung maturation indices in the amniotic fluid. Previous research is inconclusive with the lecithin/sphingomyelin (L/S) ratio being unchanged by maternal hypertensive disease in some studies [11], [12], [13] and decreased in others [14], [15].

To our knowledge, no research has been performed in preterm SGA infants to correlate the L/S ratio and lamellar body count (LBC) with Doppler ultrasound findings and maternal hypertensive disease. We hypothesize that:

  • 1)

    preterm SGA fetuses with abnormal umbilical artery Doppler ultrasound examination will have a higher L/S ratio and LBC than SGA fetuses of the same gestational age (GA) with normal umbilical artery Doppler ultrasound examination

  • 2)

    preterm SGA fetuses from mothers with HELLP syndrome will have a similar or lower L/S ratio and LBC compared to SGA fetuses of the same GA with normotensive mothers.

Section snippets

Methods

All neonates born in the Perinatal Center of the University Medical Center, Utrecht, the Netherlands, before 34 weeks of gestation are admitted to the neonatal intensive or high care unit and are prospectively collected in a database. From this database we selected all infants born between 1st January 1997 and 31st December 2003 with birth weight < 10th percentile [16] and GA < 34 weeks. GA was calculated from the last menstrual period and early sonographic examination. For the present study we

Results

In total 76 infants fulfilled the study criteria. Baseline criteria of the study population are shown in Table 1. In 62 cases amniocentesis was performed once, in the remaining cases amniocentesis was repeated. Data from the last amniocentesis before delivery was used in the analyses.

Fig. 1 shows that at each gestational age, the L/S ratio was higher in the abnormal Doppler group than in the normal Doppler group. This difference in L/S ratio was significant before and after correction for

Discussion

The present study showed that the L/S ratio of SGA fetuses is significantly higher in pregnancies with abnormal umbilical artery blood flow velocity waveform patterns (placental insufficiency) and significantly lower in pregnancies complicated by maternal hypertension. Subdivision of the maternal hypertension group showed that low L/S ratios are particularly found in pregnancies complicated by HELLP syndrome. Finally, the LBC did not differ significantly between groups in any of the analyses.

Conflict of interest statement

No financial or personal disclosures.

No funding or study sponsors.

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