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Research Article | Volume 11 Issue 3 (March, 2025) | Pages 1020 - 1029
Effect of Amnioinfusion on Perinatal Outcomes in Cases of Meconium-Stained Amniotic Fluid – A Comparative Intervention Trial in a Tertiary Care Hospital in Southern India
 ,
1
Assistant Professor, Department of Obstetrics and Gynaecology, Government Cuddalore Medical College and hospital, India
2
Final Year Postgraduate, Department of Obstetrics and Gynaecology, Government Cuddalore Medical College and Hospital, India
Under a Creative Commons license
Open Access
Received
Jan. 20, 2025
Revised
Feb. 10, 2025
Accepted
March 18, 2025
Published
March 31, 2025
Abstract
Background: Meconium-stained amniotic fluid (MSAF) is a common intrapartum finding associated with adverse perinatal outcomes, including meconium aspiration syndrome (MAS), respiratory distress, and low Apgar scores. Transcervical amnioinfusion has been proposed to dilute meconium, relieve cord compression, and improve foetal oxygenation. However, evidence from southern India remains limited. Hence, we aimed to assess the effect of intrapartum amnioinfusion on perinatal outcomes in women with moderate to thick MSAF in a tertiary care hospital in southern India. Methods: In this hospital-based comparative interventional study (November 2023–February 2024), 186 eligible women in labour with singleton term pregnancies, vertex presentation, and normal baseline cardiotocography were randomised to receive either amnioinfusion (n=93) or standard care (n=93). Outcomes included post-intervention CTG status, mode of delivery, incidence of MAS, Apgar scores, NICU admissions, and hospital stay. Data were analysed using Chi-square/Fisher’s exact tests and unpaired t-tests, with p<0.05 considered significant. Results: Post-intervention, normal CTG patterns were more frequent in the amnioinfusion group (82.8% vs. 67.7%; p=0.03). Vaginal delivery rates were higher (68.8% vs. 58.1%) and caesarean sections lower (12.9% vs. 24.7%; p=0.04) with amnioinfusion. MAS incidence was significantly reduced (4.3% vs. 17.2%; p=0.005), and fewer neonates had low Apgar scores at 1 minute (47.3% vs. 73.1%; p<0.001) and 5 minutes (23.7% vs. 45.2%; p=0.002). Mean hospital stay was shorter (2.98 ± 1.18 vs. 3.38 ± 1.29 days; p=0.03). Conclusion: Intrapartum amnioinfusion in moderate to thick MSAF significantly improves perinatal outcomes, including reducing MAS, improving Apgar scores, and lowering caesarean rates. It is a simple, effective intervention suitable for resource-limited settings.
Keywords
INTRODUCTION
Meconium-stained amniotic fluid (MSAF) is a clinical finding that is commonly encountered in labour and delivery, especially in term and post-term pregnancies, with an incidence of approximately 5–20% in total deliveries.[1] MSAF can be noted as a sign of foetal distress, although it can also occur physiologically in mature foetuses.[1] MSAF has important implications for neonatal outcomes, including increased rates of meconium aspiration syndrome (MAS), respiratory distress, and neonatal intensive care unit (NICU) admissions.[1] Around 20-30% neonates exposed to MSAF develop respiratory and neurological depression. [2] MAS is a respiratory complication that results from the aspiration of meconium-stained amniotic fluid, resulting in airway obstruction, chemical pneumonitis, surfactant inactivation, and persistent pulmonary hypertension.[3,4] Despite improvements in perinatal care, MAS remains a significant contributor to neonatal morbidity and mortality, with an incidence of 2 to 9% among neonates born through MSAF.[5] MAS remains a major contributor to neonatal morbidity, particularly in low-resource settings where neonatal intensive care capacity is limited.[4] The risk factors associated with MAS are thick meconium, non-reassuring foetal heart rate patterns, prolonged labour, 1- and 5-minute Apgar scores, and caesarean section.[3,4,6] Hence, it is necessary to prevent meconium aspiration at an early stage, in cases of meconium stained amniotic fluid or cases with risk factors to improve neonatal outcomes. One obstetric intervention which can be considered to reduce the incidence of MAS can be transcervical amnioinfusion, where isotonic fluid (typically normal saline or Ringer's lactate) is infused into the amniotic sac using an intrauterine catheter. Amnioinfusion is proposed to dilute thick meconium, reduce umbilical cord compression, improve uteroplacental perfusion, and overall prevent the foetus from inhaling thick meconium.[7] Evidence from randomized trials and meta-analyses suggests potential benefits, such as reduced MAS incidence, improved Apgar scores, and lower rates of operative deliveries, as shown in the 2021 systematic review by Davis et al. and other individual trials. [8–10] However, results have not been uniformly consistent.[11] International literature highlights that benefits may be greater in resource-constrained settings with restricted access to continuous FHR monitoring and NICU facilities, yet there is a paucity of high-quality evidence from southern India. Given the high burden of MSAF in Indian obstetric practice and the need for region-specific data, this study was designed to assess the effect of amnioinfusion on perinatal outcomes in women with moderate to thick MSAF in a tertiary care hospital in southern India.
MATERIALS AND METHODS
Study design and setting This was a hospital-based comparative interventional study conducted in the Department of Obstetrics and Gynaecology at a tertiary care teaching hospital in Cuddalore, Tamil Nadu, India. Study period The study was carried out over a period of four months, from November 2023 to February 2024. Study population The study population included pregnant women admitted in labour with moderate to thick meconium-stained amniotic fluid (MSAF). The consistency was classified based on conventional practices. [12] Inclusion criteria • Singleton pregnancies • Gestational age between 37 to 42 weeks • Vertex presentation with engaged head • Presence of moderate or thick meconium-stained liquor • Normal cardiotocography (CTG) at the time of enrolment Exclusion criteria • Multiple gestation • Major foetal anomalies • Major maternal medical or obstetric complications (e.g., preeclampsia, eclampsia, gestational diabetes requiring insulin) • Previous caesarean delivery • Intrauterine foetal death • Malpresentation • Evidence of maternal infections (ex: chorioamnionitis) Sample size calculation The sample size was estimated based on a reference study in which 55% of babies in the control group had APGAR scores >7 and 65% in the case group; with a power of 80% and confidence interval of 95%. [13] A total of 186 women were calculated as sample size (93 in each group), based on the sample size formula for comparing two proportions [14] Allocation, randomization and blinding Women meeting the inclusion criteria were enrolled and allocated into two groups in 1:1 ratio: those who received amnioinfusion (n=93) and those who received standard treatment without amnioinfusion (n=93). Eligible participants were allocated using a computer-generated, stratified, block randomization method. Randomization was stratified for gestational age (matched within less than one week), parity, and meconium consistency. Allocation was sealed in sequentially numbered opaque envelopes to ensure allocation concealment. Due to the nature of the intervention (amnioinfusion), blinding of participants and clinical staff performing the intervention were not feasible. However, efforts were made to reduce bias. Outcome assessors, including the neonatologists and staff responsible for recording neonatal outcomes (such as Apgar scores, respiratory support requirement, and NICU admission), were blinded to the group allocation. Data entry and statistical analysis were performed by an independent statistician who was blinded to the group identity, with groups labelled as Group A and Group B during analysis. Intervention The amnioinfusion group received transcervical intrapartum amnioinfusion using normal saline as per standard protocols. [15] The infusion was administered through an intrauterine catheter following the detection of meconium-stained liquor and maintained at a consistent rate. The standard treatment group was managed expectantly as per institutional protocols without amnioinfusion. Data collection Data were collected prospectively using a structured case proforma. The collected data included: 1. Socio-demographic and obstetric variables: maternal age, education, socioeconomic status, gestational age, gravida, parity, history of abortion, antenatal visits, and comorbidities (anaemia, hypertension (gestational/ overt), diabetes (gestational/ overt), maternal fever). 2. Labor and neonatal parameters: mode of labour onset, cervical dilatation at MSAF detection, Cardiotocography (CTG) findings, duration from meconium detection to delivery, total duration of labour, birth weight, sex of the baby, and blood loss. CTG was measured based on standard procedure.[16] 3. Perinatal outcomes: changes in CTG post-intervention, mode of delivery, incidence of meconium aspiration syndrome (MAS), respiratory distress, APGAR scores at 1 and 5 minutes, NICU admission and stay, oxygen/ventilatory support, perinatal death, and duration of hospital stay. [17] The following criteria was used for the diagnosis of MAS: [18–20] • Respiratory distress in newborn delivered after MSAF. • The need for oxygen to keep transcutaneous saturation above 92%. • Oxygen therapy is needed within 2 h of life for at least 12 h • The lack of malformations of the airways, lungs and heart. Statistical analysis All collected data were entered and analysed using SPSS version 25.0.[21] Continuous variables (e.g., maternal age, gestational age, birth weight, duration of labour, NICU stay) were expressed as mean ± standard deviation (SD) and compared between groups using the unpaired t-test. Categorical variables (e.g., parity, mode of delivery, MAS, CTG patterns, APGAR scores) were presented as frequencies and percentages. Group comparisons were made using the Chi-square test or Fisher's exact test where appropriate. A p-value < 0.05 was considered statistically significant. Ethical considerations Ethical approval for the study was obtained from the Institutional Ethics Committee prior to initiation of the study. Informed written consent was obtained from all participants after explaining the purpose and nature of the study.
RESULTS
The CONSORT flow diagram of the study participants is shown in Figure 1. The mean maternal age was similar in both groups (23.95 ± 3.71 years in the amnioinfusion group vs. 24.42 ± 3.92 years in the standard group; p=0.41). Educational status, socio-economic status, and parity distribution were also comparable, with the majority of participants in both groups falling into the low socio-economic category and having primary or secondary education. (Table 1) Table 1: Comparison of amnio-infusion group and standard treatment group by socio-demographic and obstetric characteristics (N=186) Variables Amnioinfusion group N=93 n (%) Standard treatment group N=93 n (%) P value Maternal age (in years) * (Mean ± S.D) 23.95 ± 3.71 24.42 ± 3.92 0.41 Educational status Illiterate 25 (26.9) 24 (25.8) 0.95 Primary 28 (30.1) 26 (28.0) Secondary 24 (25.8) 24 (25.8) Higher secondary/ graduate 16 (17.2) 19 (20.4) Socio-economic status Low 66 (71.0) 64 (68.8) 0.86 Medium 22 (23.6) 25 (26.9) High 5 (5.4) 4 (4.3) Gestational age (in weeks)* (Mean ± S.D) 39.43 ± 1.44 39.61 ± 1.42 0.39 Gravida 1 35 (37.6) 38 (40.9) 0.84 2 29 (31.2) 28 (30.1) ≥3 29 (31.2) 27 (29.0) Parity Nullipara 42 (45.2) 45 (48.4) 0.92 1 33 (35.5) 30 (32.3) ≥2 18 (19.3) 18 (19.3) History of previous abortion 13 (14.0) 16 (17.2) 0.52 Anaemia 37 (39.8) 38 (40.9) 0.96 Hypertension 18 (19.4) 20 (21.5) 0.94 Diabetes 14 (15.0) 15 (16.1) 0.83 Maternal fever 7 (7.5) 8 (8.6) 0.88 Number of ANC visits* (Mean ± S.D) 4.89 ± 2.29 5.01 ± 2.34 0.73 *Unpaired t test was used as test of significance to compare the two groups in these cases; Otherwise, chi square test was used for comparison of other variables. Obstetric variables such as mean gestational age, gravida, parity, abortions, and number of antenatal visits were statistically similar across groups. Clinical comorbidities including anaemia, hypertension, diabetes, and maternal fever were present in comparable proportions in both groups, with no significant differences. Both groups had identical proportions of induced labour (25.8%) and the consistency of meconium-stained liquor, with 61.3% showing moderate and 38.7% thick meconium in each group. The cervical dilatation at the time of meconium detection was similar (5.07 ± 1.78 cm vs. 4.95 ± 1.73 cm; p=0.64), and the CTG status prior to intervention showed a predominance of normal patterns (69.9% in both groups). Duration from meconium detection to delivery, overall labour duration, and estimated blood loss were closely balanced, with no significant differences observed. Neonatal characteristics such as sex distribution and birth weight were also similar between the groups. The mean birth weight was slightly higher in the amnioinfusion group (2828.82 ± 402.65 g vs. 2783.53 ± 395.43 g), but this difference was not statistically significant (p=0.44). (Table 2) Table 2: Comparison of amnio-infusion group and standard treatment group by labour and neonatal characteristics (N=186) Variables Amnioinfusion group N=93 n (%) Standard treatment group N=93 n (%) P value Induced labour onset 24 (25.8) 24 (25.8) 1.00 Cervical dilatation during meconium detection (cm)† (Mean ± S.D) 5.07 ± 1.78 4.95 ± 1.73 0.64 Meconium consistency Moderate 57 (61.3) 57 (61.3) 1.00 Thick 36 (38.7) 36 (38.7) CTG status before intervention* Normal 65 (69.9) 65 (69.9) 0.93 Suspicious 24 (25.8) 23 (24.7) Pathological 4 (4.3) 5 (5.4) Duration from meconium detection to delivery (in hours) † (Mean ± S.D) 4.43 ± 2.06 4.55 ± 2.02 0.69 Duration of labour (in hours) † (Mean ± S.D) 11.84 ± 4.58 12.34 ± 4.72 0.48 Blood loss during delivery (in mL) † (Mean ± S.D) 341.92 ± 142.83 357.54 ± 151.63 0.48 Sex of the baby Male 48 (51.6) 49 (52.7) 0.88 Female 45 (48.4) 44 (47.3) Birth weight (in grams) † (Mean ± S.D) 2828.82 ± 402.65 2783.53 ± 395.43 0.44 *Fischer exact t test was used as test of significance to compare the two groups in this case. †Unpaired t test was used as test of significance to compare the two groups in these cases. Otherwise, chi square test was used for comparison of other variables. Table 3 presents a comparison of perinatal outcomes between the amnioinfusion group and the standard treatment group. A higher proportion of women in the amnioinfusion group had normal CTG patterns after the intervention (82.8% vs. 67.7%; p=0.03). There was a significantly higher rate of vaginal deliveries (68.8% vs. 58.1%) and a lower rate of caesarean sections (12.9% vs. 24.7%; p=0.04) in the amnio-infusion group compared to the standard treatment group. The incidence of meconium aspiration syndrome (MAS) was significantly lower in the amnioinfusion group (4.3% vs. 17.2%; p=0.005). Similarly, APGAR scores were better in the amnioinfusion group: fewer neonates had low APGAR scores at 1 minute (47.3% vs. 73.1%; p<0.001) and at 5 minutes (23.7% vs. 45.2%; p=0.002). Although differences in respiratory distress (15.1% vs. 24.7%) and NICU admissions (16.1% vs. 25.8%) were not statistically significant, they were lower in the amnio-infusion group. Finally, the average duration of hospital stay was significantly reduced among those who received amnioinfusion (2.98 ± 1.18 days vs. 3.38 ± 1.29 days; p=0.03). Table 3: Comparison of amnio-infusion group and standard treatment group by perinatal outcomes (N=186) Variables Amnioinfusion group N=93 n (%) Standard treatment group N=93 n (%) P value CTG after intervention* Normal 77 (82.8) 63 (67.7) 0.03 Suspicious 15 (16.1) 27 (29.0) Pathological 1 (1.1) 3 (3.2) Mode of delivery Vaginal 64 (68.8) 54 (58.1) 0.04 Instrumental 17 (18.3) 16 (17.2) Caesarean section 12 (12.9) 23 (24.7) Meconium Aspiration Syndrome* 4 (4.3) 16 (17.2) 0.005 Respiratory Distress 14 (15.1) 23 (24.7) 0.11 Low APGAR score at 1 min 44 (47.3) 68 (73.1) <0.001 Low APGAR score at 5 min 22 (23.7) 42 (45.2) 0.002 Oxygen requirement* None 84 (90.3) 79 (84.9) 0.70 Oxygen 6 (6.5) 9 (9.7) CPAP 2 (2.2) 4 (4.3) Ventilator 1 (1.1) 1 (1.1) NICU admission 15 (16.1) 24 (25.8) 0.12 NICU stay duration (in days) † (Mean ± S.D) 0.54 ± 1.52 0.90 ± 2.17 <0.001 Perinatal death* 3 (3.2) 9 (9.7) 0.10 Duration of hospital stay (in days) † (Mean ± S.D) 2.98 ± 1.18 3.38 ± 1.29 0.03 *Fischer exact t test was used as test of significance to compare the two groups in this case. †Unpaired t test was used as test of significance to compare the two groups in these cases. Otherwise, chi square test was used for comparison of other variables.
DISCUSSION
In the present study, amnioinfusion was associated with a marked improvement in neonatal Apgar scores, with low Apgar at 1 minute occurring in 47.3% of the intervention group versus 73.1% in controls (p < 0.001) and low Apgar at 5 minutes in 23.7% versus 45.2% (p = 0.002). These findings align closely with multiple reports. Chattaraj et al. (2024) in West Bengal found considerable improvements in both 1- and 5-minute Apgar scores with amnioinfusion compared to usual care, while Bhosale et al. (2022) in Maharashtra noted significantly higher proportions of neonates with 1-minute Apgar > 7 and reduced need for resuscitation in the amnioinfusion group.[9,10] Similar benefits were seen in the prospective study by Parihar et al. (2020) in Madhya Pradesh, which documented a significant reduction in low Apgar scores and related neonatal depression.[22] The 2021 systematic review and meta-analysis by Davis et al., pooling data from 24 RCTs, confirmed a significant reduction in the odds of Apgar < 7 at 5 minutes with amnioinfusion. [8] The consistency across these studies likely reflects the shared mechanism of benefit from amnio-infusion: dilution of thick meconium, improved intrauterine oxygenation by relieving cord compression, and reduction of acute hypoxic stress, which directly influences early neonatal adaptation. Differences in the magnitude of effect between studies may be due to variability in baseline foetal status at enrolment, consistency (thick vs. moderate) of meconium, timing and volume of infused fluid, and quality of intrapartum monitoring. In the current study, the caesarean section rate was significantly lower in the amnioinfusion group (12.9%) compared with the standard care group (24.7%, p = 0.04), with a corresponding increase in vaginal deliveries. This is consistent with findings from Bhosale et al. (2022) in Maharashtra, who reported a marked reduction in emergency caesarean sections for foetal distress among women receiving amnioinfusion, and from Chattaraj et al. (2024) in West Bengal, where the caesarean rate fell from 36% in controls to 20% in the amnioinfusion arm. [9,10] Similarly, Parihar et al. (2020) documented a lower operative delivery rate with amnioinfusion in moderate–thick MSAF, and the 2021 Davis et al. systematic review confirmed a pooled relative reduction in caesarean delivery, particularly for suspected fetal distress. [8,22] The biological plausibility lies in amnioinfusion’s ability to relieve umbilical cord compression, reduce repetitive variable decelerations, and dilute meconium, thereby improving foetal heart rate tracings and avoiding intrapartum suspicion of hypoxia that prompts surgical delivery. In our current study, amnioinfusion was associated with fewer perinatal deaths (3.2% vs 9.7%, p=0.10), a markedly lower incidence of MAS (4.3% vs 17.2%, p=0.005), and a non-significant reduction in respiratory distress (15.1% vs 24.7%, p=0.11). Across eight comparator studies, most report concordant neonatal benefits: West Bengal (Chattaraj et al., 2024) observed reductions in MAS, respiratory distress, and special-care admissions with amnioinfusion.[9] Maharashtra case–control data (Bhosale et al., 2022) found significantly lower MAS and resuscitation needs in the amnioinfusion arm.[10] An observational series (Parihar, 2020) recorded significant reductions in low Apgar, MAS and neonatal death with amnioinfusion.[22] A single-blind RCT (Fonseca, 2017) concluded amnioinfusion reduces MAS risk.[13] A Bangladesh randomized study (Akhtar, 2022) reported less respiratory distress and fewer operative deliveries in the amnioinfusion group; and the AJOG systematic review/meta-analysis of 24 RCTs (Davis et al.) confirmed a large pooled reduction in MAS and improvements in secondary neonatal outcomes. [8,23] However, Levin et al. (Israel, 2021) found amnioinfusion independently associated with higher odds of a composite adverse neonatal outcome in a retrospective cohort.[24] This might be due to confounding by indication and severity, because AI is more often used in high-risk intrapartum scenario; South African research summarizing the CRAMP trials notes inconclusive MAS effects in resource-constrained settings with limited CTG and neonatal support. [11] Overall, our MAS reduction aligns with most trials and is biologically plausible. Amnioinfusion dilutes thick meconium, buffers cord compression, and improves gas exchange during labour, thereby reducing gasping-related aspiration and subsequent lung injury. Differences in magnitude of reduction of perinatal death and respiratory distress across studies might be explained by sample size (underpowered for mortality), baseline neonatal care capacity, and protocol variability (timing/volume/maintenance infusion). Publication bias and between-study heterogeneity documented in the meta-analysis further explain variability in findings. Strengths and limitations A key strength of this study is its robust comparative interventional design with random allocation, stratification, and allocation concealment, which minimises selection bias and balances important baseline characteristics such as gestational age, parity, and meconium consistency. The use of a structured, prospectively collected dataset ensures data completeness and consistency. Blinding of neonatal outcome assessors and the statistician reduces observer and analytical bias. The inclusion and exclusion criteria were well-defined, focusing on a clinically relevant and homogenous population, singleton, term pregnancies with moderate or thick MSAF and normal CTG at enrolment, thereby improving external validity. Adequate sample size was achieved for the primary objective reducing sampling errors. Standard operating protocols were used in delivering the intervention. The intervention was delivered by trained and experienced obstetricians as a quality control measure. The prospective nature of the study design also allowed us to establish temporality in testing the desired hypothesis of associations. Despite these strengths, the study has certain limitations. Being a single-centre trial in a tertiary care hospital limits external validity, as outcomes may differ in primary or secondary care settings with less access to continuous foetal monitoring or immediate neonatal support. Blinding of participants and intrapartum care providers was not feasible due to the nature of the intervention, potentially introducing performance bias, although outcome assessor blinding partly reduced this bias. APGAR scores and MAS adequate for detecting differences in primary neonatal outcomes such as APGAR scores and MAS, may be underpowered to detect significant differences in rarer outcomes such as perinatal mortality. Additionally, long-term neurodevelopmental outcomes of the neonates could not be assessed due to short-term follow-up nature employed in our study. Finally, while moderate and thick meconium cases were included, subgroup analyses by meconium grade or timing of amnioinfusion initiation could not performed due to limited sample size. This could have provided insight into differential effectiveness in varying clinical scenarios. Thin meconium-stained liquor cases were excluded as thick/ moderate MSAF were often associated with various complications. Thick meconium is linked with increased rates of abnormal foetal heart tracings, MAS, NICU admission, neonatal ventilation, neonatal hypoxic-ischemic encephalopathy, small for gestational age, and low Apgar scores. [1,25–28] Higher rates of caesarean delivery, puerperal endometritis, clinical chorioamnionitis, intrapartum fever, and intraamniotic infection have also been observed in women with thick MSAF.[1] However, this preference for thick MSAF comes with limited generalizability of our study findings to thick/ moderate MSAF cases. In future, cost-effectiveness evaluation on amnioinfusion as an intervention for MSAF can help in further substantiate the implementation at policy level.
CONCLUSION
In this randomized comparative study, intrapartum transcervical amnioinfusion in women with moderate to thick meconium-stained amniotic fluid significantly improved perinatal outcomes, including higher rates of normal CTG patterns, reduced caesarean delivery, lower incidence of meconium aspiration syndrome, and better Apgar scores at 1 and 5 minutes. These findings support amnioinfusion as an effective, low-cost adjunct in the intrapartum management of MSAF in resource-limited settings.
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