Ambient air pollution and the risk of pregnancy loss

Air pollution exposure in early pregnancy linked to miscarriage

Exposure to common air pollutants, such as ozone and fine particles, may increase the risk of early pregnancy loss, according to a new study.

2017 Study Abstract

Objective
To estimate the association of pregnancy loss with common air pollutant exposure. Ambient air pollution exposure has been linked to adverse pregnancy outcomes, but few studies have investigated its relationship with pregnancy loss.

Design
Prospective cohort study.

Setting
Not applicable.

Patient(s)
A total of 343 singleton pregnancies in a multisite prospective cohort study with detailed protocols for ovulation and pregnancy testing.

Intervention(s)
None.

Main Outcome Measure(s)
Timing of incident pregnancy loss (from ovulation).

Result(s)
The incidence of pregnancy loss was 28% (n = 98). Pollutant levels at women’s residences were estimated using modified Community Multiscale Air Quality models and averaged during the past 2 weeks (acute) and the whole pregnancy (chronic). Adjusted Cox proportional hazards models showed that an interquartile range increase in average whole pregnancy ozone (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.07–1.17) and particulate matter <2.5 μm (HR 1.13, 95% CI 1.03–1.24) concentrations were associated with faster time to pregnancy loss. Sulfate compounds also appeared to increase risk (HR 1.58, 95% CI 1.07–2.34). Last 2 weeks of exposures were not associated with loss.

Conclusion(s)
In a prospective cohort of couples trying to conceive, we found evidence that exposure to air pollution throughout pregnancy was associated with loss, but delineating specific periods of heightened vulnerability await larger preconception cohort studies with daily measured air quality.

More Information

  • Ambient air pollution and the risk of pregnancy loss: a prospective cohort study, Fertility and Sterility, dx.doi.org/10.1016/j.fertnstert.2017.09.037, November 16, 2017.
  • Air pollution exposure in early pregnancy linked to miscarriage, NIH study suggests, National Institutes of Health, news-releases, November 16, 2017.
  • Pregnancy loss featured image credit Heather Kittredge

Causal Association Between Primodos and Birth Defects : the EWG report

Report of the Commission on Human Medicines’ Expert Working Group on Hormone Pregnancy Tests

An Expert Working Group (EWG) of the UK’s Commission on Human Medicines (CHM) has published their report on the use of hormone pregnancy tests (HPTs) and adverse effects relating to pregnancy including possible birth defects.

Sky’s Jason Farrell confirms alleged victims of pregnancy test Primodos slam EWG report which found the drug was not responsible for serious birth defects. Campaigners say that the hormone pregnancy test review was a complete whitewash.

Commission on Human Medicines

  • Report of the Commission on Human Medicines’ Expert Working Group on Hormone Pregnancy Tests, gov.uk.
  • Referral letter for genetic testing, gov.uk.
  • Press coverage, news.google.

More About Primodos

Primodos EWG Report : Jason Farrell Reveals

Report of the Commission on Human Medicines’ Expert Working Group on Hormone Pregnancy Tests

An Expert Working Group (EWG) of the UK’s Commission on Human Medicines (CHM) has published their report on the use of hormone pregnancy tests (HPTs) and adverse effects relating to pregnancy including possible birth defects.

Sky’s Jason Farrell shares some thoughts.

Commission on Human Medicines

  • Report of the Commission on Human Medicines’ Expert Working Group on Hormone Pregnancy Tests, gov.uk.
  • Referral letter for genetic testing, gov.uk.
  • Press coverage, news.google.

More About Primodos

Perinatal BPA exposure induces chronic inflammation in offspring by modulating gut bacteria

Exposure to Bisphenol A During Pregnancy Induces Chronic Inflammation in Rabbit Offspring via Modulation of Gut Bacteria and Their Metabolites

A chemical called bisphenol A (BPA) used in plastic packaging and in the linings of food and beverage cans, may be passed from a mother to her offspring during pregnancy and cause changes in the gut bacteria of the offspring.

Emerging evidence from a research study in rabbits suggests that environmental toxicants may influence inflammation-promoted chronic disease susceptibility during early life. BPA exposure just before or after birth leads to reduced gut bacterial diversity, bacterial metabolites such as short-chain fatty acids (SCFA) and elevated gut permeability – three common early markers of inflammation-promoted chronic diseases.

The researchers observed that exposure to BPA during pregnancy caused chronic inflammation in the offspring’s intestines and liver. The researchers also noted signs of increased gut permeability – or leaky gut – and a decrease in the diversity of gut bacteria and anti-inflammatory bacterial metabolites, such as short-chain fatty acids.

2017 Study Abstract

Bisphenol A (BPA) accumulates in the maturing gut and liver in utero and is known to alter gut bacterial profiles in offspring. Gut bacterial dysbiosis may contribute to chronic colonic and systemic inflammation. We hypothesized that perinatal BPA exposure-induced intestinal (and liver) inflammation in offspring is due to alterations in the microbiome and colonic metabolome. The 16S rRNA amplicon sequencing analysis revealed differences in beta diversity with a significant reduction in the relative abundances of short-chain fatty acid (SCFA) producers such as Oscillospira and Ruminococcaceae due to BPA exposure. Furthermore, BPA exposure reduced fecal SCFA levels and increased systemic lipopolysaccharide (LPS) levels. BPA exposure-increased intestinal permeability was ameliorated by the addition of SCFA in vitro. Metabolic fingerprints revealed alterations in global metabolism and amino acid metabolism. Thus, our findings indicate that perinatal BPA exposure may cause gut bacterial dysbiosis and altered metabolite profiles, particularly SCFA profiles, leading to chronic colon and liver inflammation.

IMPORTANCE
Emerging evidence suggests that environmental toxicants may influence inflammation-promoted chronic disease susceptibility during early life. BPA, an environmental endocrine disruptor, can transfer across the placenta and accumulate in fetal gut and liver. However, underlying mechanisms for BPA-induced colonic and liver inflammation are not fully elucidated. In this report, we show how perinatal BPA exposure in rabbits alters gut microbiota and their metabolite profiles, which leads to colonic and liver inflammation as well as to increased gut permeability as measured by elevated serum lipopolysaccharide (LPS) levels in the offspring. Also, perinatal BPA exposure leads to reduced levels of gut bacterial diversity and bacterial metabolites (short-chain fatty acids [SCFA]) and elevated gut permeability-three common early biomarkers of inflammation-promoted chronic diseases. In addition, we showed that SCFA ameliorated BPA-induced intestinal permeability in vitro. Thus, our study results suggest that correcting environmental toxicant-induced bacterial dysbiosis early in life may reduce the risk of chronic diseases later in life.

Sources

  • Perinatal Bisphenol A Exposure Induces Chronic Inflammation in Rabbit Offspring via Modulation of Gut Bacteria and Their Metabolite, msystems asm, DOI: 10.1128/mSystems.00093-17, 2017 Oct.
  • Exposure to chemical during pregnancy may cause health problems for offspring, The Pennsylvania State University, story/491849, November 8, 2017.
  • Microbial responses to the perinatal bisphenol A (BPA) exposure in rabbit offspring featured image credit PMC5634791/figure/fig2, 2017 Oct 10.

IVF treatment : a healthy singleton delivery is best achieved by SET

Single-embryo transfer point – it is the way forward

In vitro fertilization (IVF) treatment in the United States is complicated by a high rate of multiple-gestation pregnancies. In 2014, the Society for Assisted Reproductive Technology reported that 23% of women <38 years of age with a pregnancy from their IVF treatment had a twin-gestation pregnancy. Although this is an improvement over past years, it remains an unacceptably high rate of twins, considering the medical risks and financial burdens associated with such pregnancies.

In this issue of Fertility and Sterility, Mersereau et al. have added strong support to the conclusion that single-embryo transfer (SET) is highly effective at reducing multiple-gestation birth rates: a 47% decrease with the use of SET compared with double-embryo transfer (DET). Furthermore, using data from their study and others, Mersereau’s team has led a revision of American Society for Reproductive Medicine committee opinion guidelines to unambiguously call for SET for women under the age of 38 years with a favorable prognosis for pregnancy. With the increasing weight of evidence and explicit professional guidelines, why is DET still so common in the United States?

In their article, Mersereau et al. report a comprehensive analysis of 10 years of national SET data, finding a 10%–15% reduction in live birth rate (LBR) with the use of SET. This reduction is not attractive to either physicians or patients, for whom IVF pregnancy rates matter a great deal. Indeed, we have shown that, despite education about the risks of twins after DET, most patients would still choose this option over SET, even with as little as a 10% drop in the LBR.

Yet we think that the 10%–15% difference in LBR may be an overestimate of the negative effect of SET on LBR, considering trends in current clinical IVF care. As reported, blastocyst transfers are becoming increasingly common, and SET live birth rates are higher with blastocysts than with cleavage-stage embryo. In fact, the LBR differences between DET and SET were still reduced, but only in the 6%–8% range, when looking at fresh blastocyst transfers in a first or second cycle. Even this may be an overestimate of the true difference between DET and SET, because higher pregnancy rates are seen when the single transferred embryo comes from a larger cohort of available embryos.

Thus, it is likely a false comparison to judge the success of SET with one or more embryos cryopreserved (at least two embryos in the cohort) against DET with one or more embryos cryopreserved (at least 3 embryos in the cohort). In a recent analysis of national IVF outcomes data, we strictly controlled for the size of the available cohort and found very similar pregnancy rates in younger good-prognosis patients undergoing elective SET versus DET on day 5–6.

We think that this trend of increasing blastocyst transfers combined with improvements in embryo selection techniques (such as preimplantation genetic screening) will result in further increases in SET pregnancy rates and allow clinics to more confidently offer SET with little to no impact on their clinic-specific pregnancy outcome. Despite continuing technical advances, however, it is likely that small but potentially significant LBR differences will persist between SET and DET if as a field we continue to report and emphasize pregnancy rates per transfer instead of cumulative pregnancy rates per fresh IVF cycle. As mentioned in Mersereau et al.’s paper, predictive models suggest that cumulative LBRs with the use of sequential SET are equal or superior to DET.

Further studies confirming this prediction will help to convince physicians, patients, and insurance providers of the benefits and feasibility of SET, even if this strategy requires additional transfers and a slightly longer time to pregnancy. A healthy singleton delivery should be the goal of all IVF cycles, and this is best achieved by SET.

Pesticides Residues Linked to Problems in Assisted Pregnancies

Association Between Pesticide Residue Intake From Consumption of Fruits and Vegetables and Pregnancy Outcomes Among Women Undergoing Infertility Treatment With Assisted Reproductive Technology

Eating fruits and vegetables high in pesticides may lower the chance of successful birth with assisted reproductive technology

2017 Study Key Points

Question
Is there an association between exposure to pesticide residues in fruits and vegetables and pregnancy outcomes?

Findings
In a cohort of 325 women undergoing infertility treatment with assisted reproductive technology, intake of high–pesticide residue fruits and vegetables was associated with a lower probability of live birth, while low–pesticide residue fruit and vegetable intake was not associated with this outcome.

Meaning
Dietary pesticide exposure within the range of typical human exposure may be associated with adverse reproductive consequences.

Abstract

Importance
Animal experiments suggest that ingestion of pesticide mixtures at environmentally relevant concentrations decreases the number of live-born offspring. Whether the same is true in humans is unknown.

Objective
To examine the association of preconception intake of pesticide residues in fruits and vegetables (FVs) with outcomes of infertility treatment with assisted reproductive technologies (ART).

Design, Setting, and Participants
This analysis included 325 women who completed a diet assessment and subsequently underwent 541 ART cycles in the Environment and Reproductive Health (EARTH) prospective cohort study (2007-2016) at a fertility center at a teaching hospital. We categorized FVs as having high or low pesticide residues using a validated method based on surveillance data from the US Department of Agriculture. Cluster-weighted generalized estimating equations were used to analyze associations of high– and low–pesticide residue FV intake with ART outcomes.

Main Outcomes and Measures
Adjusted probabilities of clinical pregnancy and live birth per treatment cycle.

Results
In the 325 participants (mean [SD] age, 35.1 [4.0] y; body mass index, 24.1 [4.3]), mean (SD) intakes of high– and low–pesticide residue FVs were 1.7 (1.0) and 2.8 (1.6) servings/d, respectively. Greater intake of high–pesticide residue FVs was associated with a lower probability of clinical pregnancy and live birth. Compared with women in the lowest quartile of high-pesticide FV intake (<1.0 servings/d), women in the highest quartile (≥2.3 servings/d) had 18% (95% CI, 5%-30%) lower probability of clinical pregnancy and 26% (95% CI, 13%-37%) lower probability of live birth. Intake of low–pesticide residue FVs was not significantly related to ART outcomes.

Conclusions and Relevance
Higher consumption of high–pesticide residue FVs was associated with lower probabilities of pregnancy and live birth following infertility treatment with ART. These data suggest that dietary pesticide exposure within the range of typical human exposure may be associated with adverse reproductive consequences.

Sources
  • Association Between Pesticide Residue Intake From Consumption of Fruits and Vegetables and Pregnancy Outcomes Among Women Undergoing Infertility Treatment With Assisted Reproductive Technology, JAMA Intern Med. doi:10.1001/jamainternmed.2017.5038, October 30, 2017.
  • Featured image credit sustainablepulse.

Pregnancy complications in patients with endometriosis

Prenatal exposure to estrogenic substances (such as DES) and environmental toxins (such as bisphenols) may increase the incidence of endometriosis in female offspring

Zullo et al. have done an extensive and thorough meta-analysis of the literature concerning endometriosis and pregnancy complications, one of the largest and most comprehensive studies to date.

Their systematic review and meta-analysis : endometriosis and obstetrics complications, provides further insight into endometriosis and pregnancy by combining the many heterogeneous studies on this topic, and it raises awareness of the many implications of endometriosis.

2017 Study Abstract

Objective
To evaluate the effect of endometriosis on pregnancy outcomes.

Design
Systematic review and meta-analysis.

Setting
Not applicable.

Patient(s)
Women with or without endometriosis.

Intervention(s)
Electronic databases searched from their inception until February 2017 with no limit for language and with all cohort studies reporting the incidence of obstetric complications in women with a diagnosis of endometriosis compared with a control group (women without a diagnosis of endometriosis) included.

Main Outcome Measure(s)
Primary outcome of incidence of preterm birth at <37 weeks with meta-analysis performed using the random effects model of DerSimonian and Laird to produce an odds ratio (OR) with 95% confidence interval (CI).

Result(s)
Twenty-four studies were analyzed comprising 1,924,114 women. In most of them, the diagnosis of endometriosis was made histologically after surgery. Women with endometriosis had a statistically significantly higher risk of preterm birth (OR 1.63; 95% CI, 1.32-2.01), miscarriage (OR 1.75; 95% CI, 1.29-2.37), placenta previa (OR 3.03; 95% CI, 1.50-6.13), small for gestational age (OR 1.27; 95% CI, 1.03-1.57), and cesarean delivery (OR 1.57; 95% CI, 1.39-1.78) compared with the healthy controls. No differences were found in the incidence of gestational hypertension and preeclampsia.

Conclusion(s)
Women with endometriosis have a statistically significantly higher risk of preterm birth, miscarriage, placenta previa, small for gestational age infants, and cesarean delivery.

Mise en garde, boîtes de Dépakote®

L’ansm agit au nom de l’Etat “pour des produits de santé sûrs, efficaces et innovants”

Récents pictogramme et mise en garde sur les boîtes dépakote®.

Image via l’ansm (agence nationale de sécurité du médicament et des produits de santé) sur Twitter.

Potential inverse association between maternal multivitamin supplement use and ASD in offspring

Antenatal nutritional supplementation and autism spectrum disorders in the Stockholm youth cohort: population based cohort study

What is already known on this topic

Evidence from observational studies is inconsistent about whether maternal supplementation with multivitamins, iron, or folic acid is protective against autism spectrum disorder (ASD) in offspring
Although the cause of autism spectrum disorder may differ by presence of intellectual disability, few studies have examined relations between nutritional supplements and ASD based on level of cognitive function

What this study adds

This population based study of a large cohort in Stockholm supported a possible inverse association between maternal use of multivitamin supplements in early pregnancy and ASD with intellectual disability in offspring compared with no maternal use of multivitamins, iron, or folic acid

2017 Study Abstract

Objective
To determine whether nutritional supplementation during pregnancy is associated with a reduced risk of autism spectrum disorder (ASD) with and without intellectual disability in offspring.

Design
Observational prospective cohort study using multivariable logistic regression, sibling controls, and propensity score matching.

Setting
Stockholm County, Sweden.

Participants
273 107 mother-child pairs identified through population registers. The study sample was restricted to children who were aged 4 to 15 years by the end of follow-up on 31 December 2011 and were born between 1996 and 2007.

Exposures
Multivitamin, iron, and folic acid supplement use was reported at the first antenatal visit.

Main outcome measure
Diagnosis of ASD with and without intellectual disability in children determined from register data up to 31 December 2011.

Results
Prevalence of ASD with intellectual disability was 0.26% (158 cases in 61 934) in the maternal multivitamin use group and 0.48% (430 cases in 90 480) in the no nutritional supplementation use group. Maternal multivitamin use with or without additional iron or folic acid, or both was associated with lower odds of ASD with intellectual disability in the child compared with mothers who did not use multivitamins, iron, and folic acid (odds ratio 0.69, 95% confidence interval 0.57 to 0.84). Similar estimates were found in propensity score matched (0.68, 0.54 to 0.86) and sibling control (0.77, 0.52 to 1.15) matched analyses, though the confidence interval for the latter association included 1.0 and was therefore not statistically significant. There was no consistent evidence that either iron or folic acid use were inversely associated with ASD prevalence.

Conclusions
Maternal multivitamin supplementation during pregnancy may be inversely associated with ASD with intellectual disability in offspring. Further scrutiny of maternal nutrition and its role in the cause of autism is recommended.

  • Antenatal nutritional supplementation and autism spectrum disorders in the Stockholm youth cohort: population based cohort study, BMJ 2017;359:j4273, 04 October 2017.
  • Featured image credit @bmj_latest.

Epilepsy drug warnings DO NOT reach enough women, 2017 survey finds

Almost 70% of women surveyed about a powerful epilepsy drug have not received new safety warnings about the dangers of taking it during pregnancy

Two thirds of women who take the antiepileptic drug sodium valproate said they had not received new safety warnings about the dangers of taking it during pregnancy, a survey carried out by epilepsy charities has found. A similar survey last year found that half of women taking the drug were unaware it could harm their fetus.

The new results are to be presented at a public hearing on the safety of valproate drugs organised by the European Medicines Agency on 26 September in London. …

… continue reading Women still not being told about pregnancy risks of valproate on The BMJ doi.org/10.1136/bmj.j4426, published 22 September 2017.
Featured image credit @bmj_latest.