New research examines link between ART and adverse birth outcomes

January 29, 2019

To address limitations in previous literature on associations between ART and worse perinatal outcomes in offspring, researchers from Finland analyzed potentially harmful effects of ART using a sibling-comparison model approach. PLUS: Consumer and personal care products and BP in pregnancy. ALSO: How can racial disparities in breastfeeding be reduced in the American South?

Parents who are having trouble conceiving may hesitate to use assisted reproductive technology (ART) because of associations between ART and worse perinatal outcomes in offspring. To address limitations in previous literature in this regard, researchers from Finland analyzed potentially harmful effects of ART using a sibling-comparison model approach. 

Published in The Lancet, the findings stem from data collected on a random sample of 20% of  Finnish households with at least one child between 0 and 14 years at the end of 2000 (n=65,723). They then analyzed birthweight, gestational age, risk of low birthweight and risk of preterm birth (PTB) among children conceived naturally and through ART (or medically assisted reproduction, the term used by the researchers). 

Differences in birth outcomes by mode of conception in the general population were estimated using standard multivariate methods that controlled for factors including multiple births, birth order and parental sociodemographic characteristics. Using a sibling comparison approach, the authors compared children conceived by ART with children conceived naturally as a way to control for all observed and unobserved factors shared by siblings.

The sample included 2,776 (4%) children who were conceived by ART between 1995 and 2000. Of them, 1,245 (natural = 620, ART = 625) were included in the within-family analysis (analyzing birth outcomes by comparing siblings born to the same parents but conceived either naturally or through medical assisted reproduction). In absolute terms, children who were conceived through ART had worse perinatal outcomes than children who were conceived naturally. 

Using between-family analysis (analyzing birth outcomes by comparing different families), the authors found that 356 of the 2,776 children (13%)conceived through ART had low birthweight (< 2500 g at birth) compared with 2189 of the 62,947 children (3%) conceived naturally. Offspring of ART were also more likely than their naturally conceived counterparts to be firstborn (1710 [62%] vs 23738 [38%]) and almost 10 times likelier to be from a multiple birth (580 [21%] vs 1365 [2%]).Using within-family analysis, the authors noticed that differences in birth outcomes were reduced but not completely eliminated. 

In linear model analysis, children conceived by ART had a difference in birthweight of -60g (95% CI -86 to -34) and a 2.15 percentage point (95% CI 1.07 to 3.24) increased risk of PTB.  In the sibling comparison, the difference in birthweight was -31 g (95% CI -85 to 22) and a 1.56 percentage point (95% CI -1.26 to 4.38) increase in risk of PTB. 

The authors noted several strengths to their study. The large dataset allowed sibling comparison, data were not prone to self-selection, and the methodological approach allowed the authors to account for unobserved parental characteristics shared by siblings. Limitations include inability to test whether the effects of ART on birth outcomes vary according to length of infertility, medication dose, or number of treatment cycles or birth order. 

Ultimately, the authors believe that it is important for parents who are considering ART to understand the risks involved. But their results, they said, suggest that while children born through ART are at an absolute higher risk for adverse birth outcomes, those risks might be attributable to factors other than the treatment.  

Consumer and personal care products and BP in pregnancy
 

Hypertension in pregnancy can lead to morbidity and mortality for mothers and their offspring. Some studies suggest that air pollution and persistent environmental chemicals may play a role in high blood pressure (BP). A new European study looked what impact chemicals widely used in consumer and personal products might have on BP in pregnancy.

Published in the International Journal of Hygiene and Environmental Health, findings from the study suggest that higher exposure to some phthalates and phenols but not pesticides may actually be associated with lower BP during pregnancy. The authors cautioned, however, that their data need to be confirmed in other studies in pregnant women.

For the research, 154 pregnant women were recruited between 2014 and 2015 as part of the Human Early-Life Exposome (HELIX) Project. HELIX is a collaborative research study designed to increase understanding of how environmental exposures (also known as the exposome) of mothers and children might influence the offsprings’ health, growth and development. Fifty-two of the women were from Spain, 46 from France, and 55 from Norway. All had uncomplicated singleton pregnancies.

The researchers collected information from the women on education level, ethnicity, pre-pregnancy weight, parity, marital status, employment status, smoking habits during pregnancy, health history, and complications of current pregnancy (hypertension, preeclampsia, eclampsia, and gestational diabetes).

The participants provided three urine samples daily over a 1 week-period in two trimesters, at around 18 and 32 weeks’ gestation. BP measurements were made at the end of the two collection weeks. The urine samples were tested for exposure to phthalates (10 metabolites), phenols (7 compounds) and organophosphate pesticides (4 metabolites). 

The authors used generalized estimating equations and linear regression to look for associations between biomarkers of exposure and the women’s BP. Exposure to some phthalate metabolites, BPA, and parabens was associated with a significant decrease in systolic and/or diastolic BP (βGEE models for systolic BP = -0.91 mmHG [95% CI: -1.65; -0.17] per doubling of BPA concentrations). The associations were more often observed in the second trimester and remained statistically significant after correction for multiple testing for BPA only. No associations were observed with organophosphate pesticides. 

Sensitivity analyses performed included eliminating data on women with pregnancy-induced hypertension (diagnosed after the second visit) and on women with conditions such as heart disease and adjusting for creatinine. 

Contrary to previous reports, these findings, the authors said, “do not support the assumption of a hypertensive effect of phthalates, phenols or OP pesticides during pregnancy,” hypothesizing that their outcomes may reflect physiological changes during pregnancy. They acknowledged the possibility of residual confounding and that they did not collect data on some risk factors for high BP, including family history of hypertension or alcohol consumption. They also noted that their data did not span the late pregnancy period, during which women are at risk for onset of hypertensive disorders. Strengths of the study that the authors noted included its repeated and prospective design and the use of multiple biospecimens from each woman.

How can racial disparities in breastfeeding be reduced in the American South?

Breastfeeding rates in the United States differ by race with rates lowest among African-American infants. These trends are especially evident in the American South. A recent study appearing Pediatrics examined how effective a hospital- and community-based initiative could be in reducing racial disparities while at the same time helping participating hospitals achieve a Baby-Friendly designation. 

Between 2014 and 2017, 33 hospitals enrolled in the CHAMPS (Communities and Hospitals Advancing Maternity Practices) program from Boston Medical Center’s Center for Health Equity, Education and Research. The program was intended to decrease racial disparities in breastfeeding by using a community and hospital collaborative strategy to improve maternity care practices and implement the Ten Steps to Successful Breastfeeding Initiative

Enrolled hospitals received intensive quality improve and technical assistance intervention to improve compliance. They were located in Mississippi (18), Louisiana (9), Texas (5), and Tennessee (2). All hospitals submitted monthly aggregate data stratified by race on breastfeeding initiation and exclusivity, skin-to-skin care, and rooming in practices. 

The authors found that the average rate of breastfeeding initiation at CHAMPS-enrolled hospitals rose from 66% to 75% and the average rate of breastfeeding exclusivity rose from 34% to 39%. The disparity between African-American and white infants in regard to breastfeeding initiation disparity decreased by 9.6% over 31 months. Among African-American infants, breastfeeding initiation and exclusivity increased from 46% to 63% and 19% to 31%, respectively. Skin-to-skin care after vaginal birth increased from 33% to 88% and care after cesarean delivery increased from 11% to 67%. Rooming in increased from 11% to 75%. 

The authors noted that skin-to-skin care after cesarean delivery was significantly associated with increased breastfeeding initiation and exclusivity overall, with the greatest impact seen among African-American infants. Rooming in was also significantly associated with increased exclusive breastfeeding among African-American infants as they were 1.54 times more likely to breastfeed than infants who did not room in (95% CI: 1.14-2.07).

By 2017, 91% of all CHAMPS hospitals, including 100% of Mississippi CHAMPS hospitals, were on the Baby-Friendly pathway and 1 hospital had gained the designation. By November 2018, 14 CHAMPS hospitals were designated Baby-Friendly. Also, during enrollment,  the number of hospitals that stopped distributing formula industry sample packs increased from 42% to 97%. 

The authors believe their findings illustrate that breastfeeding rates in the American South can be improved through implementing Baby-Friendly practices in hospitals. Their data show that increased compliance in the program was associated with a decrease in racial and/or ethnic disparities in breastfeeding initiation in hospitals and increased breastfeeding initiation, breastfeeding exclusivity, skin-to-skin care and rooming in across all races. The researchers also noted that during the implementation process, many outdated and non-evidence practices, such as breast binding, universal “trials of swallowing” with bottles of sterile water, and long periods of maternal/infant separation came to light. In addition, many evidence-based practices, such as delayed cord clamping and placing infants on their backs for safe sleep were often lacking. As hospitals worked towards improving care, these unsafe practices were eliminated and replaced with updated, evidence-based care.