Perinatal outcomes associated with meconium-stained amniotic fluid in Japanese singleton pregnancies

Introduction: We examined the perinatal outcomes in Japanese singleton pregnancies associated with meconium-stained amniotic fluid (MSAF) in relation to gestational age at delivery. Methods: We reviewed the obstetric records of all Japanese singleton deliveries after 22 weeks’ gestation managed at Japanese Red Cross Katsushika Maternity Hospital between 2002 and 2008 (n = 11,249). Results: The incidence of MSAF in the whole singleton pregnancies was 13%. The incidence of MSAF at preterm, term and postterm were 9.1%, 13% and 48%, respectively. The incidence of intrauterine fetal death, low Apgar score and low umbilical artery pH at delivery in cases with MSAF were significantly higher than those without MSAF in various gestational ages at delivery. Conclusion: Obstetric management should be affected by meconium in the amniotic fluid.


INTRODUCTION
Meconium-stained amniotic fluid (MSAF) has been reported to be associated with an obstetric hazard and significantly increase risks of adverse neonatal outcomes at term and preterm [1][2][3][4][5][6][7].Although overall risk of adverse outcome in MSAF has been reported to be low [2], MSAF is suggested to signify underlying acute or chronic fetal hypoxia [1][2][3][4][5][6][7].Recently, MSAF rates have been reported to be different among races and across gestational age [2].For example, Balchin et al. [2] observed that the incidence of MSAF in South Asian is higher than that in whites (Crude odds ratio 3.31, 95% confidence interval 1.3 -8.3, p < 0.01 by x 2 test); however there have not been well documented in MSAF in Japanese populations.In this study, we examined the perinatal outcomes in Japanese singleton pregnancies associated with MSAF in relation to gestational age at delivery.

METHODS
The protocol for this study was approved by the Ethics Committee of the Japanese Red Cross Katsushika Maternity Hospital.In addition, informed consent concerning analysis from a retrospective database was obtained from each subject.
We reviewed the obstetric records of all Japanese singleton deliveries after 22 weeks' gestation managed at Japanese Red Cross Katsushika Maternity Hospital between 2002 and 2008 (n = 11,249).The gestational age of the pregnancies were established by ultrasonographic examination of the fetal crown-rump length at 9-11 weeks' gestation.In all cases of intrauterine fetal death (IUFD), survival was checked within 2 weeks before the period of the IUFD diagnosis.The presence of MSAF was diagnosed clinically during delivery.The characteristics of perinatal outcomes such as IUFD, neonatal Apgar score at 1 and 5 minutes and umbilical artery pH were extracted from patient charts.In this study, the subjects were divided into 5 groups by gestational age at delivery as follows: those delivered at 22 -28, 29 -32, 33 -36, 37 -40 and 41 -43 weeks' gestation.
Cases and controls were compared by x 2 test for categorical variables.Odds ratios (ORs) and 95% confidence intervals (CIs) were also calculated.Differences with P < 0.05 were considered significant.
Table 2 shows the incidence of MSAF in the 5 periods of deliveries in the Japanese singleton pregnancies.As shown in Table 2, the incidence of MSAF at 33 -36 weeks was significantly lower than that at 37 -40 weeks (p < 0.01), however the incidence of MSAF at 22 -31 weeks was not different significantly from that at 37-40 weeks (p = 0.24).The incidence of MSAF at 41 -43 weeks was significantly higher than that at 37 -40 weeks (p < 0.01).Therefore, there was a 'J-shaped' relationship between MSAF and advancing gestational age, with a nadir at 33 -36 weeks' gestation.

DISCUSSION
The relationship between the presence of MSAF and increased odds for birth asphyxia and neonatal mortality is well established in preterm, term and postterm infants [1][2][3][4][5][6][7].We also found that in the infants with MSAF, the prevalence of IUFD and/or neonatal asphyxia (low Apgar scores and/or low umbilical artery pH) was increased compared with those without MSAF in Japanese singleton pregnancies in various gestational age at delivery.Therefore, obstetric management should be affected by meconium in the amniotic fluid in all periods of pregnancy beyond 22 weeks' gestation.In this study, there was a "J-shaped" relationship between MSAF and advancing gestational age, with a nadir at late-preterm (33 -36 weeks' gestation); because MSAF has been suggested to be mainly associated with fetal gastrointestinal maturity rather than hypoxia under hormonal and neural control [1,2,6].This 'J-shaped' tendency seems to be similar to some previous studies [2,6]; however the period of nadir in this study seems to be later than those in these previous studies.For example, the incidence of preterm MSAF at <33 weeks observed by Tybulewicz et al. [6] and Balchin et al. [2] were only 4.3% and 5.3%, respectively; however it was 12% in the current study.The small sample size and/or the racial differences may be possible reasons leading to the differences.One of other possible reasons may be that the current data included the cases of IUFD.In this study, for example, the incidence of MSAF in live births at <33 weeks was 9.7%.Some serious perinatal complications such as cerebral palsy and/or severe intraventricular hemorrhage have been reported to be more common in infants with preterm MSAF [5,6].Therefore, it may be reasonable that the incidence of MSAF increased in this study including IUFD as serious complication, because over half of IUFD has been reported to occur during the premature period [8].Otherwise, very premature delivery itself can be indicated as "serious complication" equivalent to IUFD.Therefore, further prospective examination may be needed to clarify the relation between MSAF and perinatal outcomes at very preterm.
At 41 -43 weeks' gestation, on the other hand, the incidence of low Apgar score and low umbilical artery pH in cases with MSAF were also significantly higher than those without MSAF.Postterm gestation itself has been suggested to be associated with the increased risk of perinatal mortality [9].The higher rate of perinatal morbidity at postterm gestation may be due to hypoxia/ acidemia associated with "relative placental insufficiency" where the placenta can no longer keep up the demands of the fetus [10].These conditions may be also associated with the presence of MSAF.In addition, when MSAF is superimposed on fetal acidemia, there is an increased risk of meconium aspiration syndrome [4].Therefore, the greater risk of adverse neonatal outcomes at ≥41 weeks in the current study support these previous suggestions especially in cases with MSAF [4,10].
In conclusion, obstetric management should be affected by meconium in the amniotic fluid in various gestational ages at delivery.Therefore, management requires awareness of this potential risk, appropriate intrapartum care and a combined obstetric-neonatal approach in cases with MSAF.

Table 1 .
The incidence of msaf in the japanese singleton pregnancies by gestational age at delivery.

Table 2 .
The incidence of MSAF in the 5 periods of delivery in the Japanese singleton pregnancies.Reference group.Values are expressed as number (%).P values by Χ2 test.OR, odds ratio; 95% CI, 95% confidence interval; IUFD, intrauterine fetal death. *

Table 3 .
The perinatal outcomes in the 5 periods of delivery in the Japanese singleton pregnancies.