Advanced maternal age and its association with placenta praevia and placental abruption: a meta-analysis

Martinelli, Katrini Guidolini; Garcia, Érica Marvila; Santos Neto, Edson Theodoro dos; Gama, Silvana Granado Nogueira da

doi:10.1590/0102-311X00206116

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REVIEW • Cad. Saúde Pública 34 (2) • 2018 • https://doi.org/10.1590/0102-311X00206116 copy

Advanced maternal age and its association with placenta praevia and placental abruption: a meta-analysis

Idade materna avançada e sua associação com placenta prévia e descolamento placentário: uma metanálise

Edad materna avanzada y su asociación con placenta previa y desprendimiento de la placenta: un metanálisis

Authorship SCIMAGO INSTITUTIONS RANKINGS

This study aimed to investigate the existence and magnitude of the association between advanced maternal age (AMA) and occurrence of placenta praevia (PP) and placental abruption (PA) among nulliparous and multiparous women, by a systematic review and meta-analysis. We searched articles published between January 1, 2005 and December 31, 2015, in any language, in the following databases: PubMed, Scopus, Web of Science, and LILACS. Women were grouped into two age categories: up to 34 years old and 35 years or older. The Newcastle-Ottawa Scale was used to evaluate the methodological quality of the studies. A meta-analysis was conducted for the PP and PA outcomes, using a meta-regression model to find possible covariates associated with heterogeneity among the studies and Egger’s test to assess publication bias. The protocol of this systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) system (CRD42016045594). Twenty-three studies met the criteria and were included in the meta-analysis. For both outcomes, an increase in age increased the magnitude of association strength, and PP (OR = 3.16, 95%CI: 2.79-3.57) was more strongly associated with AMA than PA (OR = 1.44, 95%CI: 1.35-1.54). For parity, there was no difference between nulliparous and multiparous women considered older for the PP and PA outcomes. Our review provided very low-quality evidence for both outcomes, since it encompasses observational studies with high statistical heterogeneity, diversity of populations, no control of confounding factors in several cases, and publication bias. However, the confidence intervals were small and there is a dose-response gradient, as well as a large magnitude of effect for PP.

Maternal Age; Placenta Previa; Abruptio Placentae; Pregnancy Complications

Strategy	Terms searched
1	(advanced[All Fields] AND (“maternal age”[MeSH Terms] OR (“maternal”[All Fields] AND “age”[All Fields]) OR “maternal age”[All Fields]) AND (“pregnancy outcome”[MeSH Terms] OR (“pregnancy”[All Fields] AND “outcome”[All Fields]) OR “pregnancy outcome”[All Fields])) AND (“2005/01/01”[PDAT] : “2015/12/31”[PDAT])
2	(advanced[All Fields] AND (“maternal age”[MeSH Terms] OR (“maternal”[All Fields] AND “age”[All Fields]) OR “maternal age”[All Fields]) AND adverse[All Fields] AND (“mothers”[MeSH Terms] OR “mothers”[All Fields] OR “maternal”[All Fields]) AND outcome[All Fields]) AND (“2005/01/01”[PDAT] : “2015/12/31”[PDAT])
3	(advanced[All Fields] AND (“maternal age”[MeSH Terms] OR (“maternal”[All Fields] AND “age”[All Fields]) OR “maternal age”[All Fields]) AND (“mothers”[MeSH Terms] OR “mothers”[All Fields] OR “maternal”[All Fields]) AND (“complications”[Subheading] OR “complications”[All Fields])) AND (“2005/01/01”[PDAT] : “201512/31”[PDAT])
4	(advanced[All Fields] AND (“maternal age”[MeSH Terms] OR (“maternal”[All Fields] AND “age”[All Fields]) OR “maternal age”[All Fields]) AND (“placenta praevia”[All Fields] OR “placenta previa”[MeSH Terms] OR (“placenta”[All Fields] AND “previa”[All Fields]) OR “placenta previa”[All Fields])) AND (“2005/01/01”[PDAT] : “201512/31”[PDAT])
5	(advanced[All Fields] AND (“maternal age”[MeSH Terms] OR (“maternal”[All Fields] AND “age”[All Fields]) OR “maternal age”[All Fields]) AND (“abruptio placentae”[MeSH Terms] OR (“abruptio”[All Fields] AND “placentae”[All Fields]) OR “abruptio placentae”[All Fields] OR (“placental”[All Fields] AND “abruption”[All Fields]) OR “placental abruption”[All Fields])) AND (“2005/01/01”[PDAT] : “2015/12/31”[PDAT])

Study reference for age range of the AMA group	Age range of the control group (years)	Outcome	Parity	Excludes multiple gestation	Total sample	Adjusted OR *	Location
≥ 35 years
Lamminpää et al. ³⁹39. Lamminpää R, Vehviläinen-Julkunen K, Gissler M, Selander T, Heinonen S. Pregnancy outcomes of overweight and obese women aged 35 years or older - a registry-based study in Finland. Obes Res Clin Pract 2016; 10:133-42. (2015)	< 35	PP	WPS	Yes	249,648	No	Finland
Lao et al. ⁴⁰40. Lao TT, Sahota DS, Cheng YKY, Law LW, Leung TY. Advanced maternal age and postpartum hemorrhage-risk factor or red herring? J Matern Fetal Neonatal Med 2014; 27:243-6. (2014)	20-34	PP	WPS	Yes	64,886	No	China
Pawde et al. ²¹21. Pawde AA, Kulkarni MP, Unni J. Pregnancy in women aged 35 years and above: a prospective observational study. J Obstet Gynecol India 2015; 65:93-6. (2015)	< 35	PP and PA	WPS	No	679	No	India
Alshami et al. ³⁶36. Alshami HA, Kadasne AR, Khalfan M, Iqbal SZ, Mirghani HM. Pregnancy outcome in late maternal age in a high-income developing country. Arch Gynecol Obstet 2011; 284:1113-6. (2011)	20-34	PP and PA	N	Yes	888	No	UAE
Biro et al. ³⁷37. Biro MA, Davey M-A, Carolan M, Kealy M. Advanced maternal age and obstetric morbidity for women giving birth in Victoria, Australia: a population-based study. Aust N Z J Obstet Gynaecol 2012; 52:229034. (2012)	< 35	PP and PA	N and M	No	133,357	No	Australia
Hung et al. ³⁸38. Hung TH, Hsieh CC, Hsu JJ, Lo LM, Chiu TH, Hsieh TT. Risk factors for placental abruption in an Asian population. Reprod Sci 2007; 14:59-65. (2007)	20-34	PA	WPS	Yes	36,989	Yes	Taiwan
Wang et al. ²⁵25. Wang Y, Tanbo T, Åbyholm T, Henriksen T. The impact of advanced maternal age and parity on obstetric and perinatal outcomes in singleton gestations. Arch Gynecol Obstet 2011; 284:31-7. (2011)	< 35	PA	N and M	Yes	6,619	No	Norway
35-39 and ≥ 40 years
Bateman & Simpson ¹⁵15. Bateman BT, Simpson LL. Higher rate of stillbirth at the extremes of reproductive age: a large nationwide sample of deliveries in the United States. Am J Obstet Gynecol 2006; 194:840-5. (2006)	20-34	PP and PA	WPS	No	5,163,887	No	USA
Cleary-Goldman et al. ¹¹11. Cleary-Goldman J, Malone FD, Vidaver J, Ball RH, Nyberg DA, Comstock CH, et al.Impact of maternal age on obstetric outcome. Obstet Gynecol 2005; 105(5 Part 1):983-90. (2005)	< 35	PP and PA	WPS	Yes	36,056	No	USA
Grotegut et al. ¹²12. Grotegut CA, Chisholm CA, Johnson LNC, Brown HL, Heine RP, James AH. Medical and obstetric complications among pregnant women aged 45 and older. PLoS One 2014; 9:e96237. (2014)	< 35	PP and PA	WPS	Yes	12,628,746	Yes	USA
Hung et al. ³⁴34. Hung TH, Hsieh CC, Hsu JJ, Chiu TH, Lo LM, Hsieh TT. Risk factors for placenta previa in an Asian population. Int J Gynaecol Obstet 2007; 97:26-30. (2007)	20-34	PP	WPS	Yes	37,445	Yes	Taiwan
Joseph et al. ¹³13. Joseph KS, Allen AC, Dodds L, Turner LA, Scott H, Liston R. The perinatal effects of delayed childbearing. Obstet Gynecol 2005; 105:1410-8. (2005)	20-24	PP and PA	WPS	Yes	51,084	No	Canada
Liu & Zhang ¹⁶16. Liu X, Zhang W. Effect of maternal age on pregnancy: a retrospective cohort study. Chin Med J (Engl) 2014; 127:2241-6. (2014)	25-29	PP and PA	WPS	No	57,555	No	China
Matsuda et al. ¹⁴14. Matsuda Y, Kawamichi Y, Hayashi K, Shiozaki A, Satoh S, Saito S. Impact of maternal age on the incidence of obstetrical complications in Japan: maternal age and obstetric complications. J Obstet Gynaecol Res 2011; 37:1409-14. (2011)	20-34	PP and PA	WPS	Yes	3,749	Yes	Japan
Dietl et al. ¹⁹19. Dietl A, Cupisti S, Beckmann M, Schwab M, Zollner U. Pregnancy and obstetrical outcomes in women over 40 years of age. Geburtshilfe Frauenheilkd 2015; 75:827-32. (2015)	< 30	PP	WPS	Yes	5,399	No	Germany
Blomberg et al. ¹⁰10. Blomberg M, Tyrberg RB, Kjølhede P. Impact of maternal age on obstetric and neonatal outcome with emphasis on primiparous adolescents and older women: a Swedish Medical Birth Register Study. BMJ Open 2014; 4:e005840. (2014)	25-29	PP and PA	N	Yes	374,619	No	Sweden
Carolan et al. ⁽³³ (2011)	25-29	PP	N	No	25,997	No	Australia
Ludford et al. ⁽²⁰ (2012)	25-29	PP and PA	N	Yes	34,695	No	Australia
Yang et al. ⁽³⁵ (2009)	< 20	PP and PA	N and M	Yes	1,815,843	Yes	USA
≥ 40 years
Carolan et al. ⁴¹41. Carolan MC, Davey M-A, Biro M, Kealy M. Very advanced maternal age and morbidity in Victoria, Australia: a population based study. BMC Pregnancy Childbirth 2013; 13:80. (2013)	30-34	PP	WPS	No	49,126	No	Australia
Chawanpaiboon & Hengrasmee ⁴²42. Chawanpaiboon S, Hengrasmee P. Adverse pregnancy outcomes in extremely maternal age. Open J Obstet Gynecol 2013; 3:427-34. (2013)	20-29	PP and PA	WPS	No	2,200	No	Thailand
Traisrisilp & Tongsong ⁴⁴44. Traisrisilp K, Tongsong T. Pregnancy outcomes of mothers with very advanced maternal age (40 years or more). J Med Assoc Thai 2015; 98:117-22. (2015)	20-30	PP	WPS	Yes	19,599	No	Thailand
Räisänen et al. ⁴³43. Räisänen S, Gissler M, Nielsen HS, Kramer MR, Williams MA, Heinonen S. Social disparity affects the incidence of placental abruption among multiparous but not nulliparous women: a register-based analysis of 1,162,126 singleton births. Eur J Obstet Gynecol Reprod Biol 2013; 171:246-51. (2013)	< 20	PA	N and M	Yes	1,162,126	Yes	Finland

Variables	Univariate meta-regression models				Multiple meta-regression models
Variables	Adjusted R² (%)	OR	95%CI	p-value	OR	95%CI	p-value
PP					Adjusted R² = 63.04%
Age group (years)
35-39	16.6	1.00	-		1.00	-
≥ 40	16.6	1.41	1.05-1.90	0.023	1.46	1.18-1.81	0.001
Parity
Without parity stratification	21.3	1.00	-		1.00	-
Nulliparous		1.60	1.15-2.23	0.007	1.53	1.20-1.97	0.001
Multiparous		1.23	0.77-1.96	0.375	1.26	0.90-1.74	0.168
Study with adjusted OR *
No	8.8	1.00	-		-	-
Yes	8.8	1.28	0.94-1.75	0.109	-	-	-
Exclusion of multiple gestation
No	20.0	1.00	-		1.00	-
Yes	20.0	1.47	1.08-1.99	0.015	1.44	1.15-1.81	0.003
Methodological quality of the studies
7 stars	11.9	1.00	-		-	-
8-9 stars	11.9	0.73	0.54-1.00	0.05	-	-	-
PA					Adjusted R² = 69.74%
Age group (years)
35-39	36.7	1.00	-		1.00
≥ 40	36.7	1.26	1.07-1.48	0.005	1.25	1.10-1.43	0.001
Parity
Without parity stratification		1.21	0.94-1.55	0.122	1.19	1.01-1.40	0.040
Nulliparous	13.9	1.23	0.94-1.60	0.123	1.27	1.06-1.53	0.012
Multiparous		1.00	-		1.00	-	-
Study with adjusted OR *
No	0.00	1.00	-		-	-
Yes	0.00	0.95	0.78-1.15	0.605	-	-	-
Exclusion of multiple gestation
No	0.00	1.00	-		-	-
Yes	0.00	1.04	0.85-1.28	0.685	-	-	-
Methodological quality of the studies
7 stars	4.05	1.00	-		-	-
8-9 stars	0.88	0.73-1.06	0.183	-	-	-

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[1] * Correspondence K. G. Martinelli Rua Inacio Higino 1170, apto. 608A, Vila Velha, ES 29101-094, Brasil. katrigm@gmail.com