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according to a Finnish population-based study published in JAMA. The findings may lead to changes in clinical practice, particularly for infants who may be born full term.
After adjustment for variables such as maternal age, smoking during pregnancy, any lifetime mental disorder diagnosis, and gestational age at birth, exposure to maternal antenatal corticosteroid treatment was significantly associated with mental and behavioral disorders in children, compared with nonexposure, with a hazard ratio of 1.33. Among children born at term, the adjusted hazard ratio was 1.47. Among preterm children, the hazard ratio was not significant.
“Although benefits of this therapy outweigh risks in the most vulnerable infants, this may not be true for all infants,” wrote Sara B. DeMauro, MD, an attending neonatologist and program director of the neonatal follow-up program at Children’s Hospital of Philadelphia, in an editorial also published in JAMA. “Recommendations to administer this therapy to broader populations of pregnant women may need to be reexamined until sufficient safety data, particularly among more mature infants, are available.”
Corticosteroid treatment to accelerate fetal maturation is standard care before 34 weeks’ gestation when there is a likelihood of delivery within 7 days, and studies have found that providing this therapy reduces the risk for respiratory problems when administered beyond 34 weeks. In 2016, updates to U.S. guidelines allowed for the use of corticosteroid treatment between 34 weeks and 36 weeks 6 days when women are at risk for preterm delivery within 7 days and have not received a previous course of antenatal corticosteroids.
The data from Finland indicate that “a significant number of very preterm children who might have benefited from this treatment did not receive it,” Dr. DeMauro wrote. At the same time, “45% of steroid-exposed infants were delivered at term. In these infants, minor short-term benefit may have been outweighed by significant longer-term risks. These data elucidate both the continuing struggle to accurately predict preterm birth and the incomplete uptake of an effective therapy that is beneficial when administered to the correct patients.”
Pause expanded use?
“Since the recommendations came out to expand the use of corticosteroids for preterm labor up until 37 weeks gestational age, my practice has incorporated these guidelines,” said Santina Wheat, MD, assistant professor of family and community medicine at Northwestern University in Chicago. “We have incorporated the guidelines though with the understanding that the benefits outweigh the risk. This article indicates that we may have been wrong in that understanding.” Although the association does not establish that the treatment causes mental and behavioral disorders, it “raises the question of whether we should halt this practice until additional information can be gathered,” noted Dr. Wheat, who also serves on the editorial advisory board of Family Practice News.
When administered before delivery of a very premature infant, corticosteroid therapy accelerates fetal lung maturation and helps prevent neonatal mortality, respiratory distress syndrome, and brain injury. Investigators demonstrated the benefits of antenatal corticosteroids in 1972, and the treatment – “one of the most important advances in perinatal care” – became widely used in the 1990s, Dr. DeMauro said.
To examine whether treatment exposure is associated with a risk of childhood mental and behavioral disorders and whether the risk is similar in infants born at term and preterm, Katri Räikkönen, PhD, a researcher at the University of Helsinki, and colleagues conducted a population-based retrospective study of more than 670,000 children.
The researchers identified all singleton pregnancies ending in a live birth in Finland during Jan. 1, 2006–Dec.31, 2017. In addition, they identified all consecutive maternal sibling pairs born at term, including sibling pairs discordant for maternal antenatal corticosteroid treatment exposure and sibling pairs concordant for treatment exposure or nonexposure. The investigators identified diagnoses of childhood mental and behavioral disorders using the Finnish Care Register for Health Care using ICD-10 codes on hospital inpatient and outpatient treatments by physicians in specialized medical care.
A range of disorders
In all, 670,097 infants with a median follow-up duration of 5.8 years were included in the analysis, and 14,868 (2.22%) were exposed to antenatal corticosteroids. Of the treatment-exposed children, about 45% were born at term. Of the nonexposed children, approximately 97% were born at term. Cumulative incidence rates for any mental and behavioral disorder were significantly higher for treatment-exposed children, compared with nonexposed children, in the entire cohort (12.01% vs. 6.45%; P less than .001) and in term-born children (8.89% vs. 6.31%; P less than .001).
In preterm children, the incidence rate of any mental and behavioral disorder was significantly higher among those with treatment exposure (14.59% vs. 10.71%; P less than .001). Associations persisted when the investigators focused on 241,621 sibling pairs, “suggesting that unmeasured familial confounding did not explain these associations,” the authors said.
“[In] the entire cohort and term-born children, treatment exposure ... was significantly associated with psychological development disorders; attention-deficit/hyperactivity or conduct disorders; mixed disorders of conduct and emotions, emotional disorders, disorders of social functioning or tic disorders; other behavioral or emotional disorders; and sleep disorders,” Dr. Räikkönen and colleagues reported. Among preterm-born, treatment-exposed children, the adjusted hazard ratio was significantly lower for intellectual disability and higher for sleep disorders.
Dr. DeMauro noted potential confounders in this observational study, including abnormal pregnancy events that lead clinicians to administer steroids. Such events “predispose the exposed children to adverse cognitive outcomes,” suggests some research. “Alternately, after a pregnancy at high risk for preterm delivery, families may perceive their children as vulnerable and therefore may be more likely to seek care and earlier diagnosis of mental or behavioral disorders,” Dr. DeMauro said.
The study was funded by the Academy of Finland, European Commission, Foundation for Pediatric Research, the Signe and Ane Gyllenberg Foundation, the Novo Nordisk Foundation, the Sigrid Juselius Foundation, and the Juho Vainio Foundation. The investigators and Dr. DeMauro had no conflict of interest disclosures.
SOURCE: Räikkönen K et al. JAMA. 2020;323(19):1924-33. doi: 10.1001/jama.2020.3937.
according to a Finnish population-based study published in JAMA. The findings may lead to changes in clinical practice, particularly for infants who may be born full term.
After adjustment for variables such as maternal age, smoking during pregnancy, any lifetime mental disorder diagnosis, and gestational age at birth, exposure to maternal antenatal corticosteroid treatment was significantly associated with mental and behavioral disorders in children, compared with nonexposure, with a hazard ratio of 1.33. Among children born at term, the adjusted hazard ratio was 1.47. Among preterm children, the hazard ratio was not significant.
“Although benefits of this therapy outweigh risks in the most vulnerable infants, this may not be true for all infants,” wrote Sara B. DeMauro, MD, an attending neonatologist and program director of the neonatal follow-up program at Children’s Hospital of Philadelphia, in an editorial also published in JAMA. “Recommendations to administer this therapy to broader populations of pregnant women may need to be reexamined until sufficient safety data, particularly among more mature infants, are available.”
Corticosteroid treatment to accelerate fetal maturation is standard care before 34 weeks’ gestation when there is a likelihood of delivery within 7 days, and studies have found that providing this therapy reduces the risk for respiratory problems when administered beyond 34 weeks. In 2016, updates to U.S. guidelines allowed for the use of corticosteroid treatment between 34 weeks and 36 weeks 6 days when women are at risk for preterm delivery within 7 days and have not received a previous course of antenatal corticosteroids.
The data from Finland indicate that “a significant number of very preterm children who might have benefited from this treatment did not receive it,” Dr. DeMauro wrote. At the same time, “45% of steroid-exposed infants were delivered at term. In these infants, minor short-term benefit may have been outweighed by significant longer-term risks. These data elucidate both the continuing struggle to accurately predict preterm birth and the incomplete uptake of an effective therapy that is beneficial when administered to the correct patients.”
Pause expanded use?
“Since the recommendations came out to expand the use of corticosteroids for preterm labor up until 37 weeks gestational age, my practice has incorporated these guidelines,” said Santina Wheat, MD, assistant professor of family and community medicine at Northwestern University in Chicago. “We have incorporated the guidelines though with the understanding that the benefits outweigh the risk. This article indicates that we may have been wrong in that understanding.” Although the association does not establish that the treatment causes mental and behavioral disorders, it “raises the question of whether we should halt this practice until additional information can be gathered,” noted Dr. Wheat, who also serves on the editorial advisory board of Family Practice News.
When administered before delivery of a very premature infant, corticosteroid therapy accelerates fetal lung maturation and helps prevent neonatal mortality, respiratory distress syndrome, and brain injury. Investigators demonstrated the benefits of antenatal corticosteroids in 1972, and the treatment – “one of the most important advances in perinatal care” – became widely used in the 1990s, Dr. DeMauro said.
To examine whether treatment exposure is associated with a risk of childhood mental and behavioral disorders and whether the risk is similar in infants born at term and preterm, Katri Räikkönen, PhD, a researcher at the University of Helsinki, and colleagues conducted a population-based retrospective study of more than 670,000 children.
The researchers identified all singleton pregnancies ending in a live birth in Finland during Jan. 1, 2006–Dec.31, 2017. In addition, they identified all consecutive maternal sibling pairs born at term, including sibling pairs discordant for maternal antenatal corticosteroid treatment exposure and sibling pairs concordant for treatment exposure or nonexposure. The investigators identified diagnoses of childhood mental and behavioral disorders using the Finnish Care Register for Health Care using ICD-10 codes on hospital inpatient and outpatient treatments by physicians in specialized medical care.
A range of disorders
In all, 670,097 infants with a median follow-up duration of 5.8 years were included in the analysis, and 14,868 (2.22%) were exposed to antenatal corticosteroids. Of the treatment-exposed children, about 45% were born at term. Of the nonexposed children, approximately 97% were born at term. Cumulative incidence rates for any mental and behavioral disorder were significantly higher for treatment-exposed children, compared with nonexposed children, in the entire cohort (12.01% vs. 6.45%; P less than .001) and in term-born children (8.89% vs. 6.31%; P less than .001).
In preterm children, the incidence rate of any mental and behavioral disorder was significantly higher among those with treatment exposure (14.59% vs. 10.71%; P less than .001). Associations persisted when the investigators focused on 241,621 sibling pairs, “suggesting that unmeasured familial confounding did not explain these associations,” the authors said.
“[In] the entire cohort and term-born children, treatment exposure ... was significantly associated with psychological development disorders; attention-deficit/hyperactivity or conduct disorders; mixed disorders of conduct and emotions, emotional disorders, disorders of social functioning or tic disorders; other behavioral or emotional disorders; and sleep disorders,” Dr. Räikkönen and colleagues reported. Among preterm-born, treatment-exposed children, the adjusted hazard ratio was significantly lower for intellectual disability and higher for sleep disorders.
Dr. DeMauro noted potential confounders in this observational study, including abnormal pregnancy events that lead clinicians to administer steroids. Such events “predispose the exposed children to adverse cognitive outcomes,” suggests some research. “Alternately, after a pregnancy at high risk for preterm delivery, families may perceive their children as vulnerable and therefore may be more likely to seek care and earlier diagnosis of mental or behavioral disorders,” Dr. DeMauro said.
The study was funded by the Academy of Finland, European Commission, Foundation for Pediatric Research, the Signe and Ane Gyllenberg Foundation, the Novo Nordisk Foundation, the Sigrid Juselius Foundation, and the Juho Vainio Foundation. The investigators and Dr. DeMauro had no conflict of interest disclosures.
SOURCE: Räikkönen K et al. JAMA. 2020;323(19):1924-33. doi: 10.1001/jama.2020.3937.
according to a Finnish population-based study published in JAMA. The findings may lead to changes in clinical practice, particularly for infants who may be born full term.
After adjustment for variables such as maternal age, smoking during pregnancy, any lifetime mental disorder diagnosis, and gestational age at birth, exposure to maternal antenatal corticosteroid treatment was significantly associated with mental and behavioral disorders in children, compared with nonexposure, with a hazard ratio of 1.33. Among children born at term, the adjusted hazard ratio was 1.47. Among preterm children, the hazard ratio was not significant.
“Although benefits of this therapy outweigh risks in the most vulnerable infants, this may not be true for all infants,” wrote Sara B. DeMauro, MD, an attending neonatologist and program director of the neonatal follow-up program at Children’s Hospital of Philadelphia, in an editorial also published in JAMA. “Recommendations to administer this therapy to broader populations of pregnant women may need to be reexamined until sufficient safety data, particularly among more mature infants, are available.”
Corticosteroid treatment to accelerate fetal maturation is standard care before 34 weeks’ gestation when there is a likelihood of delivery within 7 days, and studies have found that providing this therapy reduces the risk for respiratory problems when administered beyond 34 weeks. In 2016, updates to U.S. guidelines allowed for the use of corticosteroid treatment between 34 weeks and 36 weeks 6 days when women are at risk for preterm delivery within 7 days and have not received a previous course of antenatal corticosteroids.
The data from Finland indicate that “a significant number of very preterm children who might have benefited from this treatment did not receive it,” Dr. DeMauro wrote. At the same time, “45% of steroid-exposed infants were delivered at term. In these infants, minor short-term benefit may have been outweighed by significant longer-term risks. These data elucidate both the continuing struggle to accurately predict preterm birth and the incomplete uptake of an effective therapy that is beneficial when administered to the correct patients.”
Pause expanded use?
“Since the recommendations came out to expand the use of corticosteroids for preterm labor up until 37 weeks gestational age, my practice has incorporated these guidelines,” said Santina Wheat, MD, assistant professor of family and community medicine at Northwestern University in Chicago. “We have incorporated the guidelines though with the understanding that the benefits outweigh the risk. This article indicates that we may have been wrong in that understanding.” Although the association does not establish that the treatment causes mental and behavioral disorders, it “raises the question of whether we should halt this practice until additional information can be gathered,” noted Dr. Wheat, who also serves on the editorial advisory board of Family Practice News.
When administered before delivery of a very premature infant, corticosteroid therapy accelerates fetal lung maturation and helps prevent neonatal mortality, respiratory distress syndrome, and brain injury. Investigators demonstrated the benefits of antenatal corticosteroids in 1972, and the treatment – “one of the most important advances in perinatal care” – became widely used in the 1990s, Dr. DeMauro said.
To examine whether treatment exposure is associated with a risk of childhood mental and behavioral disorders and whether the risk is similar in infants born at term and preterm, Katri Räikkönen, PhD, a researcher at the University of Helsinki, and colleagues conducted a population-based retrospective study of more than 670,000 children.
The researchers identified all singleton pregnancies ending in a live birth in Finland during Jan. 1, 2006–Dec.31, 2017. In addition, they identified all consecutive maternal sibling pairs born at term, including sibling pairs discordant for maternal antenatal corticosteroid treatment exposure and sibling pairs concordant for treatment exposure or nonexposure. The investigators identified diagnoses of childhood mental and behavioral disorders using the Finnish Care Register for Health Care using ICD-10 codes on hospital inpatient and outpatient treatments by physicians in specialized medical care.
A range of disorders
In all, 670,097 infants with a median follow-up duration of 5.8 years were included in the analysis, and 14,868 (2.22%) were exposed to antenatal corticosteroids. Of the treatment-exposed children, about 45% were born at term. Of the nonexposed children, approximately 97% were born at term. Cumulative incidence rates for any mental and behavioral disorder were significantly higher for treatment-exposed children, compared with nonexposed children, in the entire cohort (12.01% vs. 6.45%; P less than .001) and in term-born children (8.89% vs. 6.31%; P less than .001).
In preterm children, the incidence rate of any mental and behavioral disorder was significantly higher among those with treatment exposure (14.59% vs. 10.71%; P less than .001). Associations persisted when the investigators focused on 241,621 sibling pairs, “suggesting that unmeasured familial confounding did not explain these associations,” the authors said.
“[In] the entire cohort and term-born children, treatment exposure ... was significantly associated with psychological development disorders; attention-deficit/hyperactivity or conduct disorders; mixed disorders of conduct and emotions, emotional disorders, disorders of social functioning or tic disorders; other behavioral or emotional disorders; and sleep disorders,” Dr. Räikkönen and colleagues reported. Among preterm-born, treatment-exposed children, the adjusted hazard ratio was significantly lower for intellectual disability and higher for sleep disorders.
Dr. DeMauro noted potential confounders in this observational study, including abnormal pregnancy events that lead clinicians to administer steroids. Such events “predispose the exposed children to adverse cognitive outcomes,” suggests some research. “Alternately, after a pregnancy at high risk for preterm delivery, families may perceive their children as vulnerable and therefore may be more likely to seek care and earlier diagnosis of mental or behavioral disorders,” Dr. DeMauro said.
The study was funded by the Academy of Finland, European Commission, Foundation for Pediatric Research, the Signe and Ane Gyllenberg Foundation, the Novo Nordisk Foundation, the Sigrid Juselius Foundation, and the Juho Vainio Foundation. The investigators and Dr. DeMauro had no conflict of interest disclosures.
SOURCE: Räikkönen K et al. JAMA. 2020;323(19):1924-33. doi: 10.1001/jama.2020.3937.
FROM JAMA
Key clinical point: Exposure to maternal antenatal corticosteroid treatment is significantly associated with mental and behavioral disorders in children, compared with nonexposure.
Major finding: After adjustment for such variables as maternal age, smoking during pregnancy, any lifetime mental disorder diagnosis, and gestational age at birth, exposure to maternal antenatal corticosteroid treatment was significantly associated with mental and behavioral disorders in children, compared with nonexposure (HR, 1.33). Among children born at term, the adjusted HR was 1.47.
Study details: A population-based retrospective cohort study that included 670,097 children in Finland.
Disclosures: The study was funded by the Academy of Finland, European Commission, Foundation for Pediatric Research, the Signe and Ane Gyllenberg Foundation, the Novo Nordisk Foundation, the Sigrid Juselius Foundation, and the Juho Vainio Foundation. The authors had no conflict of interest disclosures.
Source: Räikkönen K et al. JAMA. 2020;323(19):1924-33. doi: 10.1001/jama.2020.3937.