Amnioinfusion vs. standard management for the second trimester PPROM: a systematic review and meta-analysis of observational studies and RCTs

Figures & data

Figure 1. PRISMA 2020 flow diagram of selection process for included studies.

Figure 2. Effects of amnioinfusion on neonatal outcomes for observational studies. Forest plot of the results of the meta-analysis of observational studies for (A) latency period length, which displays the difference in latency period lengths between the amnioinfusion and standard management groups; (B) perinatal mortality rates refer to the risk ratio.

Table 1. The effects of intervention on the secondary outcomes.

Studied outcomes	Metaanalysis of observational trials					Metaanalysis of randomized studies
	Anticipated absolute effect					Anticipated absolute effect
	Studies/participants, n	RR or mean difference (95% CI)	p Value	I^2, %	Participants, n		OR or mean difference (95% CI)	p Value	I^2, %
Maternal age	3/133	−3.54 [–8.15, 1.06]	0.13	93	3/183		−0.39 [–2.03, 1.25]	.64	0
Differences in mean GA at PPROM	5/202	−2.08 [–4.18, 0.02]	0.05	89	3/183		0.11 [–0.58, 0.79]	.76	0
CRP levels at the time of PPROM	1/63	−1.55 [–2.20, −0.90]	<0.0001*	N/A			−2.43 [–4.77, −0.09]	.04	76
Differences in mean GA at delivery	5/202	2.74 [0.54, 4.93]	0.01*	80	3/183		1.31 [–1.52, 4.15]	.36	82
Differences in mean birthweight	5/202	378.12 [132.34, 623.89]	0.003*	65	3/183		76.70 [–307.94, 461.35]	.70	69
Secondary maternal and obstetric outcomes
Histological amnionitis/endometritis	1/37	0.77 [0.62, 0.97]	0.03*	N/A	N/A		N/A	N/A	N/A
Clinical chorioamnionitis	2/119	1.04 [0.57, 1.90]	0.89	0	3/182		0.68 [0.40, 1.16]	.16	4
Cesarean delivery	3/126	1.81 [1.21, 2.72]	0.004*	24	3/183		1.66 [1.01, 2.72]	.04*	0
Placenta abruptio	2/73	0.44 [0.14, 1.44]	0.08	0	3/182		6.65 [0.83, 53.05]	.07	0
Umbilical cord prolapsus	2/56	0.60 [0.08, 4.56]	0.63	0	3/181		0.80 [0.35, 1.86]	.61	0
Secondary neonatal outcomes
Short-term healthy survival	N/A	N/A	N/A	N/A	2/84		1.70 [0.62, 4.62]	.30	0
Culture proven neonatal sepsis	3/124	0.64 [0.27, 1.51]	0.30	0	3/82		0.59 [0.26, 1.35]	.21	0
Neonatal mortality	4/164	0.53 [0.27, 1.04]	0.07	62	3/183		1.06 [0.65, 1.73]	.81	49
Bronchopulmonary dysplasia	2/85	0.86 [0.08, 9.37]	0.90	19	3/95		1.26 [0.54, 2.93]	.43	N/A
Chronic lung disease	N/A	N/A	N/A	N/A	2/37		0.94 [0.44, 2.02]	.87	0
Intraventricular hemorrhage (grade III or grade IV)	1/63	0.44 [0.05, 4.04]	0.47	N/A	2/64		1.46 [0.19, 11.19]	.72	0
Necrotizing enterocolitis	N/A	N/A	N/A	N/A	2/64		2.01 [0.31, 12.89]	.46	0
Orthopedic deformities	2/84	1.45 [0.38, 5.47]	0.59	0	3/103		0.63 [0.13, 3.04]	.56	23
Pneumothorax	N/A	N/A	N/A	N/A	2/84		0.37 [0.08, 1.80]	.22	0
Composite neonatal outcome	2/85	0.66 [0.30, 1.42]	0.29	74	2/84		0.93 [0.75, 1.14]	.47	0
Long-term outcomes
Mild neurodevelopmental delay	N/A	N/A	N/A	N/A	3/43		0.69 [0.38, 1.25]	.22	0
Severe neurodevelopmental delay	N/A	N/A	N/A	N/A	2/27		0.63 [0.20, 1.97]	.79	0
Respiratory morbidities	N/A	N/A	N/A	N/A	2/25		0.93 [0.19, 4.65]	.93	0
Long-term healthy survival – best case scenario^a	N/A	N/A	N/A	N/A	2/112		1.24 [0.52, 2.92]	.63	0
Long-term healthy survival – worst case scenario^b	N/A	N/A			2/112		3.34 [0.85, 13.10]	.08	0

GA: gestational age; PPROM: preterm premature rupture of membranes; N/A: not applicable; RR: risk ratio. *refers to P value < .05.

^a Defined as: no long-term neurodevelopmental delay or no respiratory problems. Worst case scenario defined as: “if all children lost to follow up are unhealthy”.

^b Defined as: no long-term neurodevelopmental delay or no respiratory problems. Best case scenario defined as: “if all children lost to follow-up are healthy”.

Figure 3. Effects of amnioinfusion on neonatal outcomes for randomized controlled trials. Forest plot of the results of the meta-analysis of randomized control trials for (A) latency period length, which displays the difference in latency period lengths between the amnioinfusion and standard management groups; (B) perinatal mortality rates refer to the risk ratio.

Data availability statement

All data generated or analyzed during this study are included in this article and its supplementary material files. Further enquiries can be directed to the corresponding author.