Does the timing of prenatal exposure to corticosteroids and β2-agonists impact a child’s neurodevelopment by age 3?

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In a recently published study, Dr JAMA Network OpenResearchers investigated the relationship between the timing of in utero exposure to β2-agonists and corticosteroids and offspring neurodevelopmental milestones during the first three years of life.

Study: Neurodevelopmental outcomes in offspring exposed to corticosteroids and B2-adrenergic agonists in utero.  Image credit: SNeG17/
Study: Neurodevelopmental outcomes in offspring exposed in utero to corticosteroids and B2-adrenergic agonists.. Image credit: SNeG17/


Asthma is one of the leading obstructive pulmonary diseases encountered during pregnancy, and patients may require treatment to reduce complications, which would otherwise increase the risk of adverse maternal and fetal outcomes, including preterm birth, low birth weight, birth defects, and prenatal complications. Eclampsia, and perinatal death.

Thus, asthma in pregnant mothers can affect maternal and fetal health. β2-agonists and corticosteroid inhalations are prescribed for pregnant women with asthma. However, the effects of their in utero exposure on offspring neurodevelopment are clear, warranting further research.

About the study

In the current study, researchers investigated whether the timing of β2-adrenergic agonist and corticosteroid exposure during pregnancy could influence neurodevelopmental outcomes in offspring at three years of age.

The team analyzed data from participants in the Japan Environment and Children’s Study (JECS) at 15 centers in Japan. Mother-child dyads were recruited from 1 January 2011 to 31 March 2014, and data were analyzed from January to February 2023. Study exposures were β2-agonists and corticosteroids during early pregnancy (weeks 0 to 12 weeks) and midterm. Pregnancy (after 12 weeks).

Outcome measures were neurodevelopmental milestones in children (fine motor, gross motor, personal-social, communication, and problem-solving skills) assessed based on data from the Japanese Age and Stage Questionnaire, Third Edition (J-ASQ-3) at six months, 12 months, 18 months, 24 months, 30 months and three years. A sensitivity analysis was performed using the predefined mean below two standard deviations as the J-ASQ-3 domain cut-off.

Potential confounders include maternal age at delivery, education level, marital status, history of asthma before pregnancy, and alcohol intake during pregnancy; paternal and maternal smoking during pregnancy; household income; and the sex of the offspring. Additional covariates included pre-pregnancy maternal body mass index (BMI), infertility treatment, psychological distress during pregnancy, gestational diabetes, concomitant medications (such as folic acid and iron supplements and antibiotics) and child’s gestational age, birth weight, duration of breastfeeding. , and nursery attendance.

Research exposure data were obtained using two offline interviews conducted during the prenatal period by research coordinators at the regional centers. The comparison group included children whose mothers did not take anti-asthma medications during pregnancy. Multivariate logistic regression modeling using generalized estimating equations (GEEs) was performed for analysis.


Initially, 103,060 pregnancies were enrolled, and 104,062 fetuses were registered, of which 3,779 fetuses were excluded due to missing data on miscarriage, stillbirth, and live birth. Of the remaining 100,303 live births, the team excluded 8,843 births [including preterm births (before week 37.0), multiple fetuses, missing data on anti-asthmatic medication exposure at enrollment and during mid-to-late pregnancy, and post-term births (after week 41), and missing data on offspring gender, and indeterminant offspring gender].

Consequently, 91,460 maternal-fetal dyads were considered for analysis. The mean maternal age was 31 years; 4.5% of mothers smoked, 2.8% drank alcohol during pregnancy, and 11% had a prior history of asthma. Forty-nine percent (n=44,864) were female and 51% (n=46,596) were male. Most (66%) fetuses had a gestational age between 39 and 41 weeks.

More than 65% of children were breastfed during the first year of life. Among fetuses, 401 fetuses, 935 fetuses, and 568 fetuses received corticosteroid exposure during early, mid-late, and both pregnancies, respectively. β2-agonist exposure was reported for 170 (0.2%) fetuses in early pregnancy, 394 (0.4%) in mid-gestation, and 184 (0.2%) fetuses in both stages.

The team found no association between corticosteroid exposure during the two stages of pregnancy and child neurodevelopment. Similarly, no association between β2-agonist medication during early pregnancy and neurodevelopmental outcomes in the offspring has been reported. However, β2-agonist exposure during mid-late pregnancy was associated with delayed development of personal-social skills, with an odds ratio of 1.5. Sensitivity analyzes yielded similar results, indicating the robustness of the preliminary results.


Overall, the study results showed no association between β2-agonists and corticosteroids in-utero and fetal neurodevelopment regardless of exposure time, consistent with previous studies. Results indicate that pregnant asthmatics can safely receive β2-agonists and corticosteroids and do not affect neurodevelopmental outcomes in offspring. Additionally, findings may inform choices regarding maternal asthma management during pregnancy.

However, population-based studies, further studies with larger sample sizes, evaluating the relationship of anti-asthmatic drugs with fetal development, taking into account maternal asthma severity during pregnancy, drug dose, duration and route of administration, must be conducted to improve generalizability. of results.

Journal Reference:

  • Abir Nagata, PhD; Toshio Masumoto, PhD; Hidekazu Nishigori, MD, Ph.D.; Takatoshi Nakagawa, PhD; Shinji Otani, MD, PhD; Yuichi Kurozawa, PhD; Neurodevelopmental outcomes in offspring exposed to corticosteroids and B2-adrenergic agonists in utero. JAMA Network Open. 2023;6(10):e2339347. doi:10.1001/jamanetworkopen.2023.39347

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