The Journal of Maternal-Fetal & Neonatal Medicine

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Association of molar incisor hypomineralization

with premature birth or low birth weight:
systematic review and meta-analysis

Xiaoyan Wu, Jingxue Wang, Yue-heng Li, Zheng-yan Yang & Zhi Zhou

To cite this article: Xiaoyan Wu, Jingxue Wang, Yue-heng Li, Zheng-yan Yang & Zhi Zhou
(2018): Association of molar incisor hypomineralization with premature birth or low birth weight:
systematic review and meta-analysis, The Journal of Maternal-Fetal & Neonatal Medicine, DOI:
10.1080/14767058.2018.1527310

To link to this article: https://doi.org/10.1080/14767058.2018.1527310

Published online: 29 Oct 2018.

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THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
https://doi.org/10.1080/14767058.2018.1527310

REVIEW ARTICLE

Association of molar incisor hypomineralization with premature birth or low

birth weight: systematic review and meta-analysis
Xiaoyan Wua,b,c, Jingxue Wanga,b,c, Yue-heng Lia,b,c, Zheng-yan Yanga,b,c and Zhi Zhoua,b,c
a
College of Stomatology, Chongqing Medical University, Chongqing, China; bChongqing Key Laboratory for Oral Diseases and
Biomedical Science, Chongqing, China; cChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education,
Chongqing, China

ABSTRACT ARTICLE HISTORY

Objective: Molar incisor hypomineralization (MIH) is a kind of enamel hypomineralization. MIH Received 12 July 2018
has a serious negative impact on patient’s oral health. Whether neonates with premature birth Revised 11 September 2018
or low birth weight are susceptible to MIH has not been rigorously evaluated. The purpose of Accepted 19 September 2018
this systematic review and meta-analysis was to determine whether premature birth and low
KEYWORDS
birth weight increased the possibility of developing MIH in neonates. Low birth weight; meta-
Method: We searched relevant studies published from 2001 to June 2018 on PubMed and analysis; molar incisor
Embase. The methodological quality of the studies included in the meta-analysis was assessed hypomineralization;
using the Agency for Health Care Research and Quality (AHRQ) inventory tool. neonate; premature birth
Results: Premature birth promoted the prevalence of MIH (OR ¼ 1.57, 95%CI: 1.07–2.31). Low-
birth-weight neonates were approximately three times likely to suffer from MIH (OR ¼ 3.25,
95%CI: 2.28–4.62).
Conclusions: Our finding suggests that premature birth and low birth weight increase the
prevalence of MIH.

Introduction
In the late 1970s, investigations revealed that congeni-
tal enamel hypomineralization easily occurred in the
first permanent molars and incisors [1,2]. In 2001,
Weerheijm et al. [3] suggested defining this idiopathic
enamel hypomineralization as molar incisor hypomi-
neralization (MIH). MIH is a kind of enamel hypominer-
alization, refers to the developmental defects of one
or more first permanent molar enamel caused by sys-
temic factors, often involving incisors, and can be
diagnosed once erupted [4,5].
Some studies have discovered the pathological fea-
tures of MIH by scanning electron microscopy and
elemental analysis. Relative to healthy enamel, abnor-
mal accumulation of organic matter in the enamel
layer, the decrease of mineral content and the change
of microstructure caused the sharp decline of local
mechanical properties of enamel, and remarkably
reduced the hardness and elastic modulus [6–8].
Clinically, MIH often manifests as an opaque plaque
on an occlusal surface of the molar or a labial surface
of the incisor, generally not involving the dental cer-
vix. The color can be white yellow, yellowish brown,
and the boundaries with healthy enamel are clear and
irregular. In the early stage of eruption, the thickness
of the affected tooth is normal, but only the color alters.
The first permanent molar after eruption often causes
enamel disintegration due to resultant force. Dentin
exposure causes tooth sensitivity and caries, which may
rapidly progress. The affected tooth may be filled with
filling materials, and have a large filling, or it may have
been removed early [4,5,9]. These hazards have caused
great suffering to patients, affecting the quality of life
[10], and also bringing challenges to dentists [11].
In recent years, more scholars have started to put
more effort in exploring the causes of MIH [12–14].
Recent studies have found that low birth weight or
premature birth was associated with MIH [14–17].
However, other scholars found that there was no asso-
ciation between them [18–21]. Because of these con-
troversies, further research is needed to identify the
links between them. A systematic review summarizes
some of the causes associated with MIH, but these
systematic reviews are still uncertain whether low
birth weight or premature birth can lead to MIH
[22,23]. However, an in-depth understanding of this

CONTACT Zhi Zhou zhizhoucq@sina.com College of Stomatology, Chongqing Medical University, No. 426, Songshi North Road, Yubei District,
Chongqing, China
ß 2018 Informa UK Limited, trading as Taylor & Francis Group
2 X. WU ET AL.
issue is important to provide doctors with accurate
guidance to reduce tooth sensitivity due to MIH and
to prevent dental caries and enamel disintegration as
early as possible.
This study aimed to conduct a systematic review to
assess the relationship between low birth weight or
premature birth and MIH; in other words, whether a
low-birth-weight fetus or a premature neonate can be
easily susceptible to MIH.
Materials and methods
This systematic review was registered in Prospero
under the number: CRD42018094171. The concept of
MIH was proposed in 2001. Therefore, studies pub-
lished from 2001 to May 2018 were carefully retrieved.
This review was reported in accordance with the
instructions of the PRISMA statement [24]. Both of two
reviewers (X.W or J.W) who carried out the literature
search and quality evaluation had not published a
paper on this topic.
Literature search
This study did not address the severity of MIH, so the
subjects did not have an age group, and were
included according to MIH diagnosis. The main
research objective is to investigate whether low birth
weight and/or premature birth affect MIH. We
retrieved PubMed and Embase. The keywords were
(“infant, low birth weight” OR “infant, very low birth
weight” OR “infant, extremely low birth weight”) OR
(“infant, extremely premature” OR “premature birth”
OR “infant, premature”) OR (etiology) AND (hypominer-
alized AND molar) OR (molar AND hypomineralization)
OR (hypoplasia AND molar) OR MIH). Two reviewers
retrieved titles and abstracts. There was no language
restriction. In addition, manual retrieval was made to
the references of the included studies to avoid omis-
sions in database searches. If multiple studies
described the same population, the latest or the most
complete studies were used.
Criteria for inclusion/exclusion of papers
Two reviewers screened all titles, abstracts and full
texts retrieved from databases and references, and
eliminated irrelevant records. In the event of any
inconsistency, the third party author (Z.Z) would be
consulted. All observational studies were included in
this paper. Studies presenting with all of the following
criteria were considered for inclusion: (a) subjects
experienced MIH, and presented one or more of the
following conditions [25,26]: low birth weight
(<2500 g) (LBW), very low birth weight (<1500 g)
(VLBW), extremely low birth weight (<1000 g) (ELBW),
premature birth (32–37 weeks) (PT), very premature
birth (28–32 weeks) (VPT), extremely premature birth
(<28 weeks) (EPT). (b) The diagnostic criteria for MIH
are definitions related to the European Academy of
Paediatric Dentistry [4] or components of other indica-
tors [27] (such as Developmental Defects of
Enamel index).
Studies with one or more of the following condi-
tions were excluded from this review: (a) the study
only reports the deciduous molar tooth or full-mouth
tooth, no related causes of the first permanent molar
and permanent incisor. (b) Some systemic or oral local
diseases may affect the diagnosis of MIH. (c) The study
only involved the prevalence of enamel hypominerali-
zation without relevant etiological information, or we
could not extract information on MIH associated with
premature birth or low birth weight.
Data extraction
The Excel 2010 version was used to create a data
extraction table, and the two researchers independ-
ently extracted the following information: authors,
publication year, type of study, country, number of
subjects, the age of gestation, birth weight, the age of
examination, diagnostic criteria for MIH, and primary
outcome. If a study could not be understood or have
no data, the authors would be contacted by email.
Assessment of risk of bias
The risk of bias was independently performed by two
researchers (X.W and J.W). The meta-analysis included
was a cross-sectional study, so quality evaluation was
conducted in accordance with the Agency for Health
Care Research and Quality (AHRQ) Method List [28].
Eleven questions were answered. If the answer is “No”
or “Unclear”, the score of the item is “0”; if the answer
is “Yes”, the score of the item is “1”. The quality of the
study is evaluated as follows: low quality ¼ 0  3;
medium quality ¼ 4  7; high quality ¼ 8  11. Low-
quality studies would not be included in the
meta-analysis.
Data analysis
Odds ratio (OR) and 95% confidence interval (95% CI)
for low birth weight or premature birth and MIH were

obtained for the included studies. All data were ana-
lyzed using RevMan 5.3 software. The heterogeneity
was determined by using I2 effect size. I2 < 25% is con-
sidered low heterogeneity; 5% < I2 < 50% moderate
heterogeneity; I2 > 50% high heterogeneity. The result
of the merger was considered unreliable [29]. Among
the studies of the association between low birth
weight and MIH, one study was highly heterogeneous,
and had to be removed from forest map analysis [30].
To avoid the wrong conclusions caused by methodo-
logical heterogeneity, only studies with similar designs
were included in the meta-analysis, and the effect size
was adjusted and mixed. Therefore, this study only
included cross-sectional studies for meta-analysis.
Results
Studies selection results
Studies of about 1520 were found from the database
search, and one study was found by the manual
Figure 1. PRISMA flow diagram of review.
THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE 3
search, a total of 1521 studies. All studies were man-
aged in Endnote  8. After removing duplicate studies,
irrelevant studies were excluded by reading titles and
abstracts. The remaining 24 studies were read in full.
A total of 17 studies were included in the systematic
review and four studies were included in the meta-
analysis after removal of the studies with irrelevant
objective or nonfirst permanent molar or permanent
incisor. Detailed screening process is shown in
Figure 1.
Studies features
Of the 17 studies we included, seven addressed the
association between premature birth and MIH
[15,16,18,19,31–33], and four concerned the associ-
ation between low birth weight and MIH [13,14,17,34],
and four addressed the association between prema-
ture birth and low birth weight with MIH [20,21,30,35].
Some studies [17,34] showed that low birth weight
4 X. WU ET AL.
was associated with MIH. However, other studies
[13,14,20,21,30,35] confirmed that low birth weight
was not associated with MIH. Likewise, in the study of
whether premature birth can affect MIH, some studies
[15,16,30] demonstrated that premature birth was
probably associated with MIH. Nevertheless, some
studies [18–21,31–33] came to the contrary. Souza
et al. [35] found that premature birth was associated
with MIH in the group urban areas, but there was no
correlation between them in the group rural areas. In
the remaining two studies, a case-control study [36]
described the effects of very premature birth/low birth
weight and extremely premature birth/extremely low
birth weight on MIH. Another cohort study [37]
explained that very premature birth/very low birth
weight, and extremely premature birth/extremely low
birth weight did not affect MIH. Among these 6–28-
year-old subjects, the sample size was at least 82 [36]
and the largest was 3827 [30]. Most studies used
European Academy of Paediatric Dentistry as diagnos-
tic criteria [13,14,16,17,20,21,30–36], and four studies
used Developmental Defects of Enamel index
[15,18,19,37] (Table 1).
Assessment of risk of bias
Risk assessments were performed on three cross-sec-
tional studies included in the meta-analysis. There
were no studies with less than seven points. Quality
evaluation was summarized in Table 2.
Meta-analysis
After removing one highly heterogeneous study, we
performed a meta-analysis of a small number of stud-
ies including statistical effects. Due to the small num-
ber of studies, no subgroup analysis was conducted.
The heterogeneity was not high, and no metaregres-
sion analysis was required. Quantitative assessment of
publication bias was not performed using an Egger
test or a funnel plot.
The association between PT and MIH
Meta-analysis of the association between PT and MIH
was involved in two cross-sectional studies [19,30].
There was no heterogeneity between the two studies
(I2 ¼ 0%). Therefore, fixed effect models were used.
Results revealed that PT promoted the prevalence of
MIH (OR ¼ 1.57, 95%CI: 1.07–2.31; Figure 2).
The association between LBW and MIH
After the heterogeneity analysis removed one study
[30], the OR values and 95% confidence intervals of
the two cross-sectional studies [17,34] were finally
combined, and the heterogeneity was low (I2 ¼ 20%).
The results showed that low-birth-weight neonates
were approximately three times likely to have MIH
(OR ¼ 3.25, 95%CI: 2.28–4.62; Figure 3).
Narrative synthesis
The meta-analysis could not be performed because
there were no OR value or its confidence interval for
the same design of two or more studies addressing
the association between VP with VLBW or LBW and EP
with ELBW and MIH. We descriptively analyzed the
results as follows.
The association of VPT with VLBW or LBW
and MIH
Nelson et al. [37] found that for very premature neo-
nates with very low birth weight (VPT with VLBW), the
enamel opacity of the permanent incisors and the first
permanent molars was significantly increased com-
pared with the full-term neonates (p ¼ .03), but could
not impact hypomineralization (p ¼ .65). Brogardh
et al. believed that for very premature neonates with
low birth weight (VPT with LBW), an increase of 100 g
per body weight could reduce the number of MIH
cases by 4.5% (p ¼ .006). In general, very premature
birth (with very low birth weight or low birth weight)
increased the prevalence of MIH, but due to differen-
ces in experimental design and diagnostic criteria
between the two studies, we were unable to com-
bine them.
The association of EPT with ELBW and MIH
For MIH in very premature birth infants with very low
birth weight, Nelson et al. [37] found that compared
with full-term teenagers, EPT with ELBW did not cause
an increase in the incidence of the first permanent
molar’s demarcated opacity (p ¼ .32) and hypoplasia
(p ¼ .85). The authors believe that the reason may be
that very premature neonates, who have special
needs, are likely to receive dental services than chil-
dren without special needs. However, another study
[36] published in the same year showed that every
additional week of gestational age reduced the inci-
dence of MIH by 9.6%, which had a significant impact
on MIH (p ¼ .003). At present, the conclusions of these
Table 1. Characteristics of studies included in systematic review.
Severity of Severity of Age evaluation, year Diagnostic
Author, year Study style Country Participants (n) gestational time birthweight (mean or range) criteria of MIH Results and conclusion
Gurrusquieta Cross-sectional Mexico 1,156 schoolchildren – LWB Mean age EAPD Low birth weight significantly associated
et al. 574 boys 582 girls of 8.4 ± 1.6 years with the presence of MIH, ORadj ¼ 2.575,
2017 [17] 95% CI: 1.502–4.414, p ¼ .001
Tourino et al. Cross-sectional Brazil 1,181 schoolchildren PT – 8 and EAPD No significant associations were found
2016 [33] 466 boys 474 girls 9 years, 11 months between Premature birth and MIH, crude
PR ¼ 1.46, 95% CI: 0.99–2.16, p ¼ .054
Hysi et al. Cross-sectional Albania 1,575 schoolchildren PT – 8–10 years EAPD There was no statistical differences between
2016 [32] 831 boys 744 girls MIH and PT, ORuadj ¼ 1.05, 95% CI:
0.31–3.61, p ¼ .940
Garot et al. Case-control French 849 patients PT – 6 and 28 years EAPD There was no association between prema-
2016 [31] turity and MIH. ORadj ¼ 1.7, 95% CI:
0.6–5.3, p ¼ .3
de Lima et al. Cross-sectional Brazil 594 schoolchildren 219 PT – 11–14 years EAPD PT was associated with the presence of
2015 [16] boys 375 girls MIH, PRaju ¼ 1.82, 95% CI:
1.24–2.18, p ¼ .02
Pitiphat et al. Cross-sectional Thailand 282 schoolchildren 134 PT LWB Mean age EAPD There was no association of preterm birth
2014 [21] boys 148 girls of 8.0 ± 0.5 years (p ¼ .20) and low birth weight (p ¼ .06)
with MIH
Allazzam et al. Cross-sectional Saudi Arabia 267 children 134 males PT LWB Mean age EAPD There was no association low birth weight
2014 [20] and 133 females of 9.4 ± 1.38 years. (p ¼ .908) and preterm birth (p ¼ .972)
with MIH
Souza et al. Cross-sectional Brazil 1,151 children 527 – LWB Mean age of EAPD LBW was not associated with the presence
2013 [14] boys and 624 girls 8.86 ± 1.28 years. of MIH, ORuadj ¼ 0.72, 95% CI:
0.38–1.38, p ¼ .40
onmez et al.
S€ Cross-sectional Turkey 3,827 children PT LWB Mean age EAPD MIH was found to be associated with pre-
2013 [30] of 9.55 years maturity, ORuadj ¼ 1.538 0,95 %CI:
1.03–2.297, p ¼ .035, without LBW,
ORuadj ¼ 1.179 0,95 %CI:
0.738–1.884, p ¼ .49
Ghanim et al. Cross-sectional Iraqi 823 schoolchildren – LWB 10–12 years EAPD LBW was associated with the presence of
2013 [34] MIH, ORadj ¼ 3.87, 95% CI:
2.42–6.17, p < .0001
Souza et al. Cross-sectional Brazil 903 schoolchildren 395 PT LWB Aged 6–12 years old, EAPD Birth weight showed no significant associ-
2012 [35] boys 508 girls and living in urban ation with MIH, Group UA: LWB
(Group UA) and ORuadj ¼ 0.65 0,95 %CI: 0.31–1.36,
rural (Group p ¼ .260 PT ORuadj ¼ 0.13,95%CI:
RA) areas 0.18–0.96, p ¼ .046 Group RA: LWB
ORuadj ¼ 1.08 0,95 %CI: 0.47–2.43,
p ¼ .853 PT ORuadj ¼ 2.72,95%CI:
0.88–8.38, p ¼ .081
Ahmadi et al. Cross-sectional Iran 433 children 215 boys PT – 7–9 years old DDE index Birth prematurity were more prevalent in
2012 [15] and 218 girls. children affected by MIH in current study.
(p < .001)
Nelson et al. Cohort study America 224 children 105 boys VP/VLBW, mean birthweight was Mean age of DDE Index VP/VLBW or EP/ELBW was not related to
2011 [37] and 99 girls 1272.9 g, mean gestational age was 15.0 ± 0.77 years Enamel hypoplasia or of incisors and first
30.5 weeks EP/ELBW, mean birth- molar teeth
weight was 977.1 g, mean gestational
THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE

age was 27.5 weeks

(continued)
5
 6

Table 1. Continued.
Severity of Severity of Age evaluation, year Diagnostic
Author, year Study style Country Participants (n) gestational time birthweight (mean or range) criteria of MIH Results and conclusion
Brogardh et al. Case-control Sweden 82 children 42 boys VP/LBW, mean birthweight was Mean age of 11.3 years EDPA Both low birth weight (ORuadj ¼ 0.955 0,95
2011 [36] 40 girls 1654.1 g, mean gestational age was in both group %CI: 0.924–0.987, p ¼ .006) and low ges-
31.0 weeks EP/ELBW, mean birth- tational age (ORuadj ¼ 0.904 0,95 %CI:
X. WU ET AL.

weight was 870.8 g, mean gestational 0.845–0.967, p ¼ .003) had an impact

age was 26.5 weeks on MIH
Arrow 2009 [19] Cross-sectional Australia 550 children PT – 9–10 years DDE Index No significant associations were found
between Premature birth and enamel
defects of the first permanent molars
(ORadj ¼ 1.96, 95%CI: 0.57–6.67, p ¼ .28)
Whatling and Case-control UK 109 children 46 boys – LWB Mean age of 8.7 years EDPA No associations were found with MIH and
Fearne and 63 girls LBW, ORuadj ¼ 2.88 0,95 %CI:
2008 [13] 0.73–11.29, p ¼ .13,
Dietrich et al. Case-control Germany 2408 pupils PT – 10–17 years DDE Index No significant divergence was found in
2003 [18] terms of the preterm birth among the
children of the test group versus the
control group, The low return, however,
precluded any definitive interpretation of
these results.
LBW: low birth weight; PT: prematurity; MIH: Molar Incisor Hypomineralization; EAPD: European Academy of Paediatric Dentistry; DDE index: Developmental Defects of Enamel index; ORadj: odds ratio adjusted;
ORuadj: odds ratio unadjusted; Group UA: Group urban area; Group RA: Group rural area.

Table 2. Agency for Health Care Research and Quality (AHRQ) quality assessment summary.
Assessments
for quality Any patient Response
Study Sample Time Subjective assurance exclusions Missing rates and
Author, year style Definition selection period Consecution components purposes from analysis Confounding data completeness Follow-up Score/11
Gurrusquieta et al. 2017 [17] CS 1 1 1 1 1 1 0 1 0 0 0 7
Sonmez et al. 2013 [30] CS 1 1 1 1 1 1 1 1 0 1 0 9
Ghanim et al. 2013 [34] CS 1 1 1 1 1 1 1 1 0 1 0 9
Arrow 2009 [19] CS 1 1 1 1 1 1 1 1 1 1 0 10

Figure 2. Forest plot with meta-analysis evaluation of the association between prematurity (PT) and MIH by mean of Odds Ratio
and I2.
Figure 3. Forest plot with meta-analysis evaluation of the association between low birth weight (LBW) and MIH by mean of Odds
Ratio and I2.
two studies are not uniform. Long-term studies are
required to confirm whether the prevalence of MIH
would be increased by EPT.
Discussion
In this systematic review and meta-analysis, we
assessed the risk of PT and LBW individuals develop-
ing into MIH, emphasized clear classification and
dimensional diagnosis, and provided evidence of
strong associations, and narratively summarized the
effects of VPT with VLBW or LBW and EPT with ELBW
on MIH. In two cross-sectional studies [19,30],
reviewers evaluated 4377 subjects. They found that PT
indeed caused MIH (OR ¼ 1.57, 95%CI: 1.07–2.31;
Figure 2). LBW individuals are three times likely to be
diagnosed as MIH (OR ¼ 3.25, 95%CI: 2.28–4.62;
Figure 3). Nevertheless, whether VPT with VLBW or
LBW and EPT with ELBW can cause a high prevalence
of MIH is not known from the existing data. This sys-
tematic review is the first attempt to quantify meta-
analysis to compare MIH risk in patients affected by
PT or LBW and healthy patients. According to the I2
test, we used the fixed-effect model to merge OR and
95% CI. Compared with the random effect model, it is
usually a more accurate method and the results
obtained are more reliable. In our review, we found a
link of PT and LBW with MIH, which is different from
the findings of the systematic review by Silva et al.
[23]. This system synthesis was based on the conclu-
sion that the combined effect quantity was not
obtained, which was contrary to the results of Taylor’s
systematic review [38]. This may be due to the choice
THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE 7
of different study types, but cross-sectional studies are
very important study based on large-area populations,
and their importance cannot be ignored.
MIH is an enamel disease. It is the maturity of the
enamel of the first permanent molar and permanent
incisor from the last trimester to one year old. The
demarcated opacity may be induced by long-term or
sudden attacks by enamel-forming cells, which causes
severe interference with secretory ameloblasts [39].
This has a significant effect on changes in enamel for-
mation and maturation. A recent study [40] also
showed that during development, ameloblasts could
form enamel with normal thickness, but the enamel
maturation ability was greatly reduced, eventually
developing into MIH. However, what causes these
changes is still unknown. Industrialization in the west-
ern world may be a contributing factor to MIH. An
early study [41] in North Africa showed that MIH was
rare in North Africa with a prevalence of only 1.1%.
However, last year’s study on the prevalence of MIH
[42] showed that the prevalence of MIH has reached
14.4% worldwide. An appropriate dental care strategy
is urgently needed to take care of these patients and
determine the cause of MIH to prevent it.
Different degrees of premature birth and different
grades of low body weight are usually analyzed as
separate MIH-related factors, but they are interrelated
and premature neonates are often associated with
low birth weight [37]. Premature birth and its compli-
cations [43,44] lead to poor health in premature neo-
nates. In addition, the pain and uncomfortable
feeling induced by untreated MIH prevent children
from eating and eventually leads to impaired health.
8 X. WU ET AL.
Fortunately, researchers have come to realize in
recent years that there may be some differences
between premature birth and full-term birth in terms
of MIH [36]. Over time, MIH will aggravate, and its
adverse consequences will become severe. The erup-
tion of incisors is characterized by demarcated opa-
city, which affects the appearance, and then
aggravates the sensitivity or caries. For the first per-
manent molar, enamel disintegration, caries and rapid
development often show residual roots at a young
age. The management of MIH is also a complex and
continuous process [45,46]. I hope that our conclu-
sions can cause everyone to pay enough attention to
the association between premature birth and low
body weight with MIH. It is expected to avoid the
occurrence of some MIH by reducing premature birth
and low-birth-weight neonates through multifield
cooperation.
Advantages and limitations of the review
This systematic review is the first attempt to quantita-
tively analyze the association between PT/LBW and
MIH. There are very few systematic reviews deeply
addressing the effect of these two factors on MIH. In
this study, we conducted a comprehensive search to
ensure the comprehensiveness of the studies, and
implemented strict inclusion and exclusion to ensure
that the diagnosis of the first permanent molar with
or without incisor hypomineralization. The studies
with consistent design are selected for combination. If
the heterogeneity is small, the conclusions will be reli-
able. In the studies we have included, there are a
wide range of regions, including Europe (such as
France, Germany, Sweden), North America (such as
USA, Mexico), Asia (such as Thailand, Turkey, Iran) and
Oceania (Australia).
This systematic review and meta-analysis have the
following limitations and may result in publication
bias. The main limitation is that the studies included
in the meta-analysis are cross-sectional studies with
a low level of evidence. The number of studies that
reported the adjusted effect size was insufficient.
The number of studies we included was small.
Moreover, studies with positive results were easy to
be submitted, which may also lead to publica-
tion bias.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This study was supported by the Chongqing Municipal
Health and Family Planning Commission in 2017
[2017ZDXM018] and two other projects [2018MSXM036,
2018QNXM023].
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