Maternal exposure to air pollution and risk of autism in

children: A systematic review and meta-analysis.

Chun H, et al. Environ Pollut. 2020.

Show full citation

Abstract
BACKGROUND: The number of children diagnosed with autism spectrum disorder
(ASD) has been increasing. Previous studies suggested potential association between
pregnancy air pollution exposure and ASD. This systematic review and meta-analysis is
intended to summarize the association between maternal exposure to outdoor air
pollution and ASD in children by trimester based on recent studies.

METHODS: A systematic literature search in 3 databases (Medline, Embase, and Web

of Science) was performed using subject headings related to ASD and air pollution
since 2007. Eligible studies were screened and evaluated based on predetermined
criteria. For meta-analyses, the studies were grouped by air pollutant and exposure time
(prenatal period and trimesters). Within-group studies were standardized by log odds
ratio (OR) and then combined by three meta-analysis methods: frequentist fixed and
random effects models, and Bayesian random effects model.

RESULTS: Initial search identified 1564 papers, of which 25 studies remained for final
analysis after duplicates and ineligible studies were removed. Of the 25 studies, 13, 14,
12, and 7 studies investigated ASD in children associated with PM2.5, PM10, NO2, and
ozone, respectively. The frequentist and Bayesian random effects models resulted in
different statistical significance. For prenatal period, frequentist meta-analysis returned
significant pooled ORs with 95% confidence intervals, 1.06(1.01,1.11) for PM2.5 and
1.02(1.01,1.04) for NO2, whereas Bayesian meta-analysis showed similar ORs with
wider 95% posterior intervals, 1.06(1.00,1.13) for PM2.5 and 1.02(1.00,1.05) for NO2.
Third trimester appeared to have higher pooled ORs for PM2.5, PM10, and ozone, but
patterns in the time-varying associations over the trimester were inconsistent.

CONCLUSIONS: For positive association between maternal exposure to ambient air

pollution and ASD in children, there is some evidence for PM2.5, weak evidence for
NO2 and little evidence for PM10 and ozone. However, patterns in associations over
trimesters were inconsistent among studies and among air pollutants.
Systematic review of areca (betel nut) use and adverse
pregnancy outcomes.
De Silva M, et al. Int J Gynaecol Obstet. 2019.

Show full citation

Abstract
BACKGROUND: Betel nut is the fourth most commonly abused substance worldwide
and has been associated with significant adverse health outcomes. Little is known about
its effects on the fetus.

OBJECTIVE: To perform a systematic review of studies investigating prenatal betel nut

use and adverse perinatal outcomes.

SEARCH STRATEGY: Pubmed, Embase, and Cochrane databases were searched

from inception until July 2018 using the terms areca, betel nut, pregnancy, pregnancy
complications, and infection.

SELECTION CRITERIA: Eligible studies included case-control, cohort, and randomized

control studies involving pregnant women.

DATA COLLECTION AND ANALYSIS: Where appropriate, bivariate meta-analysis was

performed, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.

MAIN RESULTS: In total, 28 studies were screened and eight studies (including 15 270
women) were included in the review and meta-analysis. Preterm birth, low birthweight,
and anemia were most commonly investigated. Meta-analysis revealed a significant
association between betel nut use and low birthweight, with a pooled OR of 1.75 (95%
CI, 1.35-2.27).
CONCLUSIONS: The review identified only eight eligible studies, all based in the Asia-
Pacific region. There was a significant association between low birthweight and betel
nut exposure in pregnancy. Further prospective studies are needed to confirm this
association.

Effect of age at first use of oral contraceptives on breast

cancer risk: An updated meta-analysis.
Ji LW, et al. Medicine (Baltimore). 2019.
Show full citation

Abstract
BACKGROUND: We evaluated the relationship between the age at first use of oral
contraceptives (OC) and breast cancer (BC) risk.

METHODS: We searched PubMed, Embase, and related reviews published through

June 28, 2018, and used summary relative risk (RR) and 95% confidence intervals (CIs)
to evaluate the cancer risks, and fixed-effects dose-response meta-analysis to assess
potential linear and non-linear dose-response relationships.

RESULTS: We included 10 studies, with 8585 BC cases among 686,305 participants.

The pooled RR for BC was 1.24 (95% CI: 1.10-1.41), with moderate heterogeneities (I = 
66.5%, P < .001). No significant publication bias was found (P = .584 for Begg test, P 
= .597 for Egger test). A linear dose-response relationship between the age at first OC
use and BC risk was detected (P = .518 for non-linearity). Subgroup analyses were
restricted to studies done by BC subtypes, region, sample size, follow-up time and study
quality. Inconsistent consequences with no statistical significance were explored when
limited to studies from Western countries, study quality <7, sample size <10,000, follow-
up time <5 years, and BC subtypes defined by estrogen receptor (ER), progesterone
receptor (PR) and human epidermal growth factor receptor-2 (HER-2) expression status
in tumor tissue. Sensitivity analyses indicated that our results were stable and reliable
after removing each study in turn and omitting studies of adjusted unreported variables.

CONCLUSION: A significant linear relationship between the age at first OC use and BC
risk was confirmed. No further consistent differences are noted in multiple aspects of
BC subtypes defined by progesterone or ER status.

Effects of repeat prenatal corticosteroids given to

women at risk of preterm birth: An individual participant
data meta-analysis.
Crowther CA, et al. PLoS Med. 2019.

Show full citation

Abstract
BACKGROUND: Infants born preterm compared with infants born at term are at an
increased risk of dying and of serious morbidities in early life, and those who survive
have higher rates of neurological impairments. It remains unclear whether exposure to
repeat courses of prenatal corticosteroids can reduce these risks. This individual
participant data (IPD) meta-analysis (MA) assessed whether repeat prenatal
corticosteroid treatment given to women at ongoing risk of preterm birth in order to
benefit their infants is modified by participant or treatment factors.

METHODS AND FINDINGS: Trials were eligible for inclusion if they randomised women
considered at risk of preterm birth who had already received an initial, single course of
prenatal corticosteroid seven or more days previously and in which corticosteroids were
compared with either placebo or no placebo. The primary outcomes for the infants were
serious outcome, use of respiratory support, and birth weight z-scores; for the children,
they were death or any neurosensory disability; and for the women, maternal sepsis.
Studies were identified using the Cochrane Pregnancy and Childbirth search strategy.
Date of last search was 20 January 2015. IPD were sought from investigators with
eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration.
IPD were analysed using a one-stage approach. Eleven trials, conducted between 2002
and 2010, were identified as eligible, with five trials being from the United States, two
from Canada, and one each from Australia and New Zealand, Finland, India, and the
United Kingdom. All 11 trials were included, with 4,857 women and 5,915 infants
contributing data. The mean gestational age at trial entry for the trials was between 27.4
weeks and 30.2 weeks. There was no significant difference in the proportion of infants
with a serious outcome (relative risk [RR] 0.92, 95% confidence interval [CI] 0.82 to
1.04, 5,893 infants, 11 trials, p = 0.33 for heterogeneity). There was a reduction in the
use of respiratory support in infants exposed to repeat prenatal corticosteroids
compared with infants not exposed (RR 0.91, 95% CI 0.85 to 0.97, 5,791 infants, 10
trials, p = 0.64 for heterogeneity). The number needed to treat (NNT) to benefit was 21
(95% CI 14 to 41) women/fetus to prevent one infant from needing respiratory support.
Birth weight z-scores were lower in the repeat corticosteroid group (mean difference
-0.12, 95%CI -0.18 to -0.06, 5,902 infants, 11 trials, p = 0.80 for heterogeneity). No
statistically significant differences were seen for any of the primary outcomes for the
child (death or any neurosensory disability) or for the woman (maternal sepsis). The
treatment effect varied little by reason the woman was considered to be at risk of
preterm birth, the number of fetuses in utero, the gestational age when first trial
treatment course was given, or the time prior to birth that the last dose was given.
Infants exposed to between 2-5 courses of repeat corticosteroids showed a reduction in
both serious outcome and the use of respiratory support compared with infants exposed
to only a single repeat course. However, increasing numbers of repeat courses of
corticosteroids were associated with larger reductions in birth z-scores for weight,
length, and head circumference. Not all trials could provide data for all of the
prespecified subgroups, so this limited the power to detect differences because event
rates are low for some important maternal, infant, and childhood outcomes.

CONCLUSIONS: In this study, we found that repeat prenatal corticosteroids given to

women at ongoing risk of preterm birth after an initial course reduced the likelihood of
their infant needing respiratory support after birth and led to neonatal benefits. Body
size measures at birth were lower in infants exposed to repeat prenatal corticosteroids.
Our findings suggest that to provide clinical benefit with the least effect on growth, the
number of repeat treatment courses should be limited to a maximum of three and the
total dose to between 24 mg and 48 mg.

Ulipristal acetate for uterine fibroids: a systematic

review and meta-analysis.
Review article

Kalampokas T, et al. Gynecol Endocrinol. 2016.

Show full citation

Abstract
Ulipristal acetate (UA), a selective progesterone modulator, has been approved for
short-term therapy for symptomatic fibroids. We decided to undertake a systematic
review of the best available evidence and draw a more definitive conclusion regarding
the efficacy of UA for the management of uterine fibroids. The outcomes included
symptomatic relief, quality of life-related parameters, reduction in fibroid size, side
effects and recurrence rate. We included four randomised controlled trials which
consisted of three trials which compared UA with placebo, and one trial compared it with
gonadotropin-releasing hormone analogues for symptomatic relief. The three trials
comparing UA with placebo reported significant improvement in symptoms related to
excessive uterine bleeding as evidenced by the attainment of amenorrhea or reduction
in pictorial blood assessment chart. However, due to the heterogeneity of the available
data, a meta-analysis was possible only for one the outcomes - attainment of
amenorrhea which indicated improvement in symptoms [57.88 (19.81-169.16); p < 
0.00001]. The improved quality of life parameters and reduction in fibroid size was
noted in the UA group. With regards to adverse events, even though the three included
studies reported increased non-physiological endometrial-related changes following UA,
these changes reverted back to normal within 6 months. Short-term use of UA seems to
be an effective and safe method of treating uterine fibroids.

Importance of the delivery-to-insertion interval in

immediate postpartum intrauterine device insertion: A
secondary analysis.
Lerma K, et al. Int J Gynaecol Obstet. 2020.

Show full citation

Abstract
OBJECTIVE: To evaluate the delivery-to-insertion interval for copper postpartum
intrauterine devices (PPIUDs).

METHODS: Secondary analysis of two related studies at five academic sites in India

from March 2015 to July 2016. IUDs were inserted within 48 hours of vaginal delivery.
Women (n=560) were grouped by whether they underwent postplacental (≤10 minutes)
or immediate (>10 minutes) insertion. Outcomes were complete expulsion at the 6-8-
week follow-up (primary), and IUD-to-fundus distance, as assessed by postinsertion
ultrasound (secondary).

RESULTS: Overall, 93 (16.6%) women received a postplacental PPIUD and 467

(83.4%) received an immediate PPIUD. Complete expulsion at follow-up was 3.2%
(n=3) in the postplacental and 7.5% (n=35) in the immediate postpartum group
(P=0.176; difference in proportions, 4.3%; 95% confidence interval, -2.0 to 8.1).
Distance from the fundus did not differ between the two groups (P=0.107); high fundal
placement (≤10 mm from the internal endometrial verge) was achieved for most women.

CONCLUSION: The present data challenge previous guidance on the timing of PPIUD

insertion. The 10-minute insertion window is a barrier to uptake and should be
reassessed for inclusion in service delivery guidelines. A flexible interval would
accommodate the multiple post-delivery tasks of providers and increase access to
PPIUD.
Improvement of cardiac function in fetuses with growth
restriction following antenatal betamethasone
administration: fact or artifact?
Vadivelu P, et al. J Matern Fetal Neonatal Med. 2019.

Show full citation

Abstract
INTRODUCTION: Use of corticosteroids for fetal lung maturation has reduced the
perinatal mortality/morbidity from prematurity related complications. There is a paucity
of studies evaluating the effect of steroid administration on the fetal circulation and
cardiac function in fetal growth restriction (FGR). The aim of the study was to assess
changes in fetal Doppler indices and cardiovascular function in pregnancies
complicated with FGR after administration of betamethasone.

METHODS: This was a prospective study conducted in a tertiary care research center

between July 2017 and May 2018. Pregnant women with FGR between 28 and 36
weeks' gestation, who were scheduled to receive betamethasone (two doses of 12 mg,
24 h apart) were recruited. Fetal cardiovascular function in fetuses FGR was assessed
immediately before first dose and once between 6 and 24 h after the second dose of
betamethasone by the same operator. Wilcoxon matched-pairs signed-rank test or
paired t-tests were used to compare parameters before and after corticosteroid
exposure.

RESULTS: Fifty cases with FGR were evaluated before and after administration of
betamethasone, at mean gestational age of 34.6 ± 2.0 weeks. Fetal heart rate (148.78 ± 
9.10 versus 144.73 ± 9.61, p < .001), left heart myocardial performance index ([MPI],
0.66 ± 0.06 versus 0.55 ± 0.09, p ≤ .001) and right heart MPI (0.65 ± 0.04 versus 0.63 ± 
0.04, p .016) showed improvement after steroids. Left heart isovolumic relaxation and
contraction indices along with ejection time of both sides showed a small but statistically
significant improvement (p < .001), but other fetal cardiac functional and Doppler indices
remain unchanged after steroids.

CONCLUSIONS: Fetal heart rate, cardiac MPI, left sided isovolumic indices showed an
improvement after betamethasone administration. Follow up studies are needed to
ascertain whether these effects persist in the long term and to determine whether these
are beneficial to a growth restricted fetuses.