Analysis of neonatal mortality risk factors in Brazil: a systematic review and meta-analysis of observational studies

Veloso, Felipe Camilo Santiago; Kassar, Liliana de Meira Lins; Oliveira, Michelle Jacintha Cavalcante; Lima, Telmo Henrique Barbosa de; Bueno, Nassib Bezerra; Gurgel, Ricardo Queiroz; Kassar, Samir Buainain

doi:10.1016/j.jped.2018.12.014

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Review articles • J. Pediatr. (Rio J.) 95 (5) • Sep-Oct 2019 • https://doi.org/10.1016/j.jped.2018.12.014 copy

Analysis of neonatal mortality risk factors in Brazil: a systematic review and meta-analysis of observational studies^☆ ☆ Please cite this article as: Veloso FC, Kassar LM, Oliveira MJ, Lima TH, Bueno NB, Gurgel RQ, et al. Analysis of neonatal mortality risk factors in Brazil: a systematic review and meta-analysis of observational studies. J Pediatr (Rio J). 2019;95:519-30.

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective:

To identify, using a systematic review and meta-analysis of observational studies, which risk factors are significantly associated with neonatal mortality in Brazil, and to build a comprehensive national analysis on neonatal mortality.

Sources:

This review included observational studies on neonatal mortality, performed between 2000 and 2018 in Brazilian cities. The MEDLINE, Elsevier, Cochrane, LILACS, SciELO, and OpenGrey databases were used. For the qualitative analysis, the Newcastle-Ottawa Scale was used. For the quantitative analysis, the natural logarithms of the risk measures and their confidence intervals were used, as well as the DerSimonian and Laird method as a random effects model, and the Mantel-Haenszel model for heterogeneity estimation. A confidence level of 95% was considered.

Summary of findings:

The qualitative analysis resulted in six studies of low and four studies of intermediate-low bias risk. The following exposure factors were significant: absence of partner, maternal age ≥35 years, male gender, multiple gestation, inadequate and absent prenatal care, presence of complications during pregnancy, congenital malformation in the assessed pregnancy, Apgar < 7 at the fifth minute, low and very low birth weight, gestational age ≤ 37 weeks, and caesarean delivery.

Conclusion:

The most significant risk factors presented in this study are modifiable, allowing aiming at a real reduction in neonatal deaths, which remain high in the country.

KEYWORDS
Neonatal mortality; Risk factors; Brazil; Review systematic; Meta-analysis

	Analyzed studies	Year	City/State	Study type	Number of subjects	Analyzed variables
I	Lansky et al.³3 Lansky S, Lima Friche AA, Silva AA, Campos D, Azevedo Bittencourt SD, Carvalho ML, et al. Birth in Brazil survey: neonatal mortality, pregnancy and childbirth quality of care. Cad Saude Publica. 2014;30:S192-207.	2014	Several cities in the five Brazilian macro-regions	Cohort	24,329	Maternal schooling \| Maternal marital status \| Maternal age \| Newborn's gender \| Previous stillbirth \| Type of pregnancy \| Adequacy of prenatal care \| Complications during pregnancy \| Birth weight \| Congenital malformation \| Apgar at the 5th minute
II	Lima et al.¹⁷17 Lima EdeF, Sousa AI, Griep RH, Primo CC. Fatores de risco para mortalidade neonatal no município de Serra, Espírito Santo. Rev Bras Enferm. 2012;65:578-85.	2012	Serra/ES	Cohort	32,275	Maternal schooling\| Maternal age \| Type of pregnancy \| Adequacy of prenatal care \| Birth weight \| Type of delivery
III	Zanini et al.¹³13 Zanini RR, de Moraes AB, Giugliani ER, Riboldi J. Determinantes contextuais da mortalidade neonatal no Rio Grande do Sul por dois modelos de análise. Rev Saude Publica. 2011;45:79-89.	2011	35 micro-regions/RS	Cohort	138,407	Previous stillbirth \| Birth weight \| Congenital malformation \| Apgar in the 5th minute \| Gestational age \| Type of delivery
IV	Garcia et al.¹⁶16 Garcia LP, Fernandes CM, Traebert J. Risk factors for neonatal death in the capital city with the lowest infant mortality rate in Brazil. J Pediatr (Rio J). 2019;95:194-200.	2019	Florianópolis/SC	Cohort	15,879	Adequacy of prenatal care \| Birth weight \| Congenital malformation \| Apgar in the 5th minute \| Type of delivery \| Gestational age
V	Almeida and Barros¹²12 Almeida SD, Barros MB. Atenção à saúde e mortalidade neonatal: estudo caso-controle realizado em Campinas, SP. Rev Bras Epidemiol. 2004;7:22-35.	2004	Campinas/SP	Case-control	351	Birth weight \| Gestational age
VI	Nascimento et al.¹¹11 Nascimento RM, Leite ÁJ, Almeida NM, Almeida PC, Silva CF. Determinantes da mortalidade neonatal: estudo caso-controle em Fortaleza, Ceará, Brasil. Cad Saude Publica. 2012;28:559-72.	2012	Fortaleza/CE	Case-control	396	Newborn's gender \| Adequacy of prenatal care \| Birth weight \| Gestational age
VII	Kassar et al. ⁶6 Kassar SB, Melo AM, Coutinho SB, Lima MC, Lira PI. Determinants of neonatal death with emphasis on health care during pregnancy, childbirth and reproductive history. J Pediatr (Rio J). 2013;89:269-77.	2013	Maceió/AL	Case-control	408	Adequacy of prenatal care \| Birth weight
VIII	Schoeps et al. ¹⁴14 Schoeps D, Almeida MF, Alencar GP, França I, Novaes HM, Siqueira AA, et al. Fatores de risco para mortalidade neonatal precoce. Rev Saude Publica. 2007;41:1013-22.	2007	São Paulo/SP	Case-control	459	Maternal marital status \| Adequacy of prenatal care \| Complications during pregnancy \| Birth weight \| Gestational age
IX	Paulucci and Nascimento¹⁵15 Paulucci RS, Nascimento LF. Mortalidade neonatal em Taubaté: um estudo caso-controle. Rev Paul Pediatr. 2007;25:358-63.	2007	Taubaté/SP	Case-control	392	Birth weight \| Congenital malformation
X	Mendes et al.¹⁸18 Mendes KG, Olinto MT, Costa JS. Case-control study on infant mortality in Southern Brazil. Rev Saude Publica. 2006;40:240-8.	2006	Caxias do Sul/RS	Case-control	354	Adequacy of prenatal care \| Birth weight \| Type of delivery \| Gestational age

Analyzed variables	Factors	Analyzed studies	Adjusted OR	95% CI
Maternal schooling	Complete Elementary School (8-11 years)	(3) (17)	4.24 0.92	[1.61-11.16] [0.59-1.41]
	Incomplete Elementary School (4-7 years)	(3) (17)	3.60 0.94	[1.43-9.07] [0.60-1.47]
Maternal marital status	Mother without a partner	(3) (14)	2.49 1.80	[1.69-3.66] [1.00-3.00]
Maternal age	Maternal age ≥ 35 years	(3) (17)	1.62 1.54	[0.95-2.78] [1.04-2.29]
Newborn's gender	Male gender	(3) (11)	1.49 2.09	[1.08-2.05] [1.09-4.03]
Previous stillbirth	Presence of previous stillbirth	(3) (13)	3.62 1.29	[2.05-6.41] [1.01-1.65]
Type of pregnancy	Multiple pregnancy	(3) (17)	4.79 2.26	[2.37-9.68] [1.03-4.96]
Adequacy of prenatal care	Inadequate prenatal care	(3) (11) (6) (14) (16) (18)	2.84 2.03 2.49 2.00 3.04 1.45	[1.44-5.62] [1.03-3.99] [1.14-5.40] [2.00-3.50] [1.61-5.97] [0.44-4.77]
Adequacy of prenatal care	Absence of prenatal care	(14) (17)	16.10 3.48	[4.70-55.40] [1.86-6.49]
Complications during pregnancy	Presence of complications during pregnancy	(3) (14)	6.07 8.20	[3.85-9.55] [5.00-13.50]
Birth weight	Birth weight between 1500 and 2499 g	(3) (17) (13)	5.19 2.36 5.46	[2.44-11.04] [1.46-3.83] [4.07-7.31]
	Birth weight less than 1500 g	(3) (17) (13)	32.27 5.49 41.15	[12.65-82.35] [2.52-11.96] [29.25-57.87]
	Birth weight less than 2500 g	(12) (11) (6) (14) (15) (16) (18)	3.84 14.75 2.57 17.30 22.80 9.46 34.60	[1.18-12.50] [5.26-41.35] [1.16-5.72] [8.40-35.60] [7.52-69.12] [4.06-23.60] [3.84-311.50]
Congenital malformation	Presence of congenital malformation	(3) (13) (15) (16)	16.55 14.79 12.91 6.12	[6.47-42.38] [11.18-19.59] [2.13-78.38] [2.14-15.67]
Apgar at the 5th minute	Presence of Apgar score < 7 at the 5th minute	(3) (13) (16)	15.79 11.39 19.08	[6.54-38.14] [8.51-15.25] [8.78-42.92]
Gestational age	Gestational age < 37 weeks	(12) (11) (14) (13) (16) (18)	5.37 3.41 8.80 1.84 6.09 43.46	[1.83-17.98] [1.09-4.03] [4.30-17.80] [1.42-2.39] [2.58-15.23] [10.26-83.97]
Type of delivery	Caesarean delivery	(17) (13) (18)	1.52 0.80 2.36	[1.17-1.97] [0.68-0.93] [0.70-7.61]

Analyzed studies	Selection	Comparability	Outcome	Total	Classification
Cohort
(3)	***	*	***	7/9	High quality
(17)	***	*	***	7/9	High quality
(13)	***	*	***	7/9	High quality
(16)	***	*	***	7/9	High quality
Case-control
(12)	***	*	**	6/9	Intermediate-high quality
(11)	***	*	**	6/9	Intermediate-high quality
(6)	***	*	**	6/9	Intermediate-high quality
(14)	***	*	**	6/9	Intermediate-high quality
(15)	***	*	***	7/9	High quality
(18)	***	*	***	7/9	High quality

FACTORS	Studies included in the analysis	Total number of analyzed subjects	Final adjusted OR	Final (95%) CI	p	I ²	p
Complete elementary school (8-11 years)	(3) (17)	56,604	1.853	[0.417-8.241]	0.005	87.4%	0.418
Incomplete elementary school (4-7 years)	(3) (17)	56,604	1.727	[0.466-6.400]	0.010	84.8%	0.414
Mother without partner^b b Indicates significant factor(s).	(3) (14)	24,788	2.236	[1.630-3.068]	0.344	0.0%	<0.001
Maternal age ≥ 35 years^b b Indicates significant factor(s).	(3) (17)	56,604	1.568	[1.141-2.154]	0.882	0.0%	0.006
Male gender^b b Indicates significant factor(s).	(3) (11)	24,725	1.591	[1.193-2.121]	0.362	0.0%	0.002
Presence of previous stillbirth	(3) (13)	162,736	2.090	[0.762-5.733]	0.001	90.6%	0.152
Multiple pregnancy^b b Indicates significant factor(s).	(3) (17)	56,604	3.361	[1.612-7.009]	0.163	48.7%	0.001
Inadequate prenatal care^b b Indicates significant factor(s).	(3) (11) (6) (14) (16) (18)	41,825	2.182	[1.761-2.703]	0.771	0.0%	<0.001
Absence of prenatal care^b b Indicates significant factor(s).	(14) (17)	32,734	6.799	[1.534-30.147]	0.030	78.8%	0.012
Presence of complications during pregnancy^b b Indicates significant factor(s).	(3) (14)	24,788	6.961	[4.979-9.733]	0.381	0.0%	<0.001
Birth weight between 1500 and 2499 g	(3) (17)^a a Indicates studies that were a source of heterogeneity in each analysis. (13)	195,011	5.424	[4.128-7.126]	0.902	0.0%	<0.001
Birth weight < 1500 g^b b Indicates significant factor(s).	(3) (17)^a a Indicates studies that were a source of heterogeneity in each analysis. (13)	195,011	39.995	[29.026-55.109]	0.603	0.0%	<0.001
Birth weight < 2500 g^b b Indicates significant factor(s).	(12)^a a Indicates studies that were a source of heterogeneity in each analysis. (3) (6)^a a Indicates studies that were a source of heterogeneity in each analysis. (14) (15) (16) (18)	18,239	15.519	[9.997-24.092]	0.684	0.0%	<0.001
Presence of congenital malformation^b b Indicates significant factor(s).	(3) (13) (15) (16)	179,007	14.025	[10.849-18.132]	0.402	0.0%	<0.001
Presence of Apgar score < 7 at the 5th minute^b b Indicates significant factor(s).	(3) (13) (16)	178,615	12.397	[9.545-16.102]	0.417	0.0%	<0.001
Gestational age < 37 weeks^b b Indicates significant factor(s).	(12) (11)^a a Indicates studies that were a source of heterogeneity in each analysis. (14) (13)^a a Indicates studies that were a source of heterogeneity in each analysis. (16) (18)^a a Indicates studies that were a source of heterogeneity in each analysis.	155,846	7.130	[4.329-11.742]	0.706	0.0%	<0.001
Caesarean delivery^b b Indicates significant factor(s).	(17)^a a Indicates studies that were a source of heterogeneity in each analysis. (13) (18)	171,036	1.551	[1.202-2.000]	0.480	0.0%	0.001

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[1] * Corresponding author. E-mail:samirbkr@uol.com.br (S.B. Kassar).