Early treatment with SSRIs can increase the overall risk of fetal malformations, especially heart malformations.Late pregnancy treated with
Early treatment with SSRIs can increase the overall risk of fetal malformations, especially heart malformations.
Late pregnancy treated with SSRIs may increase the risk of preterm birth and neonatal complications, and is associated with neurodevelopmental disorders in children, especially in autism spectrum disorders (ASD). The use of fluoxetine and Pa Rossi Dean should be avoided in the early stage of pregnancy, and the teratogenic risk is higher than that of other SSRIs.
Over the past ten years, the impact of SSRIs on pregnant women and newborns has received increasing attention. SSRIs currently on the market include Ai Sciplan, Hide Saki, citalopram, fluoxetine, sertraline and Pa Rossi Dean, chemical structure and pharmacological effects of each drug is different, there are differences in the effects on the fetus. Previous studies have focused on the effects of SSRIs on maternal and fetal outcomes, while ignoring the unique reproductive toxicity of each SSRI. The only exception is Pa Rossi Dean, because of its potential risk of fetal heart defects is more clear, FDA has issued a warning: early pregnancy with the use of Pa Rossi Dean can lead to increased risk of fetal teratogenic.
In view of the above, the researchers Alwan S and other reproductive risk for a variety of SSRI systematic review, designed to provide more specific information for medical staff and patients. The study was published online May 2nd in CNS Drugs, the following is the main points:
First, early pregnancy exposure / escitalopram citalopram
1 congenital malformation
Two cohort studies showed that early pregnancy using citalopram can increase in the overall risk of all malformations, but another study said, due to the risk of birth defects is the mother's depression itself, instead of drugs. Some studies show that about the use of infant urinary system abnormality and citalopram. A large Finland study found that early pregnancy using citalopram and neural tube defects and congenital malformations of digestive system related. NBDPS case-control study, increase the frequency of use of citalopram in early pregnancy associated with birth defects, including anencephaly, craniosynostosis, omphalocele.
2 cardiovascular abnormalities
Early pregnancy using citalopram is widely considered associated with congenital heart disease, particularly heart ventricular septal defect; when the drug exposure before organ confined formation, no elevated risk of heart disease. Study in Australia, early pregnancy exposure to citalopram and patent ductus arteriosus (FDAs) associated with an increased risk of.
The Danish study shows that pregnancy 30 days before pregnancy in citalopram / escitalopram can increase the risk of miscarriage (hazard ratio OR=1.43, 95%CI=1.34-1.53). However, when the study population was limited to patients diagnosed with depression, the correlation disappeared, suggesting that there were confounding factors other than drugs. A recent analysis also shows that in the first 35 weeks of pregnancy and abortion / prescription of escitalopram citalopram is associated with an increased risk (OR=1.29 95%CI=1.21-1.37; citalopram, escitalopram OR=1.25, 95%CI=1.09-1.42). However, 3-12 months prior to pregnancy, not the use of drugs during pregnancy, is also associated with an increased risk of miscarriage, suggesting that a higher risk of miscarriage may be maternal depression, rather than the drug itself.
Two, early exposure to fluoxetine
1, congenital malformation
Clear that fluoxetine can increase the risk of congenital malformations, including cardiac abnormalities, gastrointestinal tract, ear, face, neck, congenital malformation craniosynostosis, omphalocele. A Canadian study found 81 also received fluoxetine and benzene two nitrogen 䓬 treatment of pregnant offspring increased risk of congenital malformations, and 638 received fluoxetine in the treatment of pregnant women is not, that cause congenital malformations may be more severe depression, rather than drugs.
A study in Australia has shown that early pregnancy with fluoxetine, in addition to heart abnormalities, also increases the risk of gastrointestinal malformations, ear, face, or neck malformations in infants. NBDPS case-control study showed that craniosynostosis baby's mother, early pregnancy received fluoxetine treatment was higher than that in the control group mothers, and exposed to fluoxetine and anencephaly, craniosynostosis, omphalocele was significantly related to the risk of early closure of the cranial suture increased nearly doubled (OR=1.9, 95%CI=1.1-3.0).
2 cardiovascular abnormalities
Fluoxetine can increase the risk of cardiac malformations, especially ventricular septal defect, atrial septal defect, and right ventricular outflow tract stenosis.
In a prospective cohort study, exposure to fluoxetine in early pregnancy is associated with cardiac malformations in infants, especially in patients with ventricular septal defect and atrial septal defect. A small, prospective cohort study in Israel has shown that the use of SSRIs in pregnant women in early pregnancy, including fluoxetine, can double the risk of heart defects in infants. NBDPS case-control study and other studies showed that the use of fluoxetine during pregnancy was significantly associated with right ventricular outflow tract stenosis (OR=2.0, 95%CI=1.4-3.1).
Fluoxetine can cause an increase in the rate of miscarriage, but the related research is limited. The Danish record linkage study showed that pregnancy within 35 days before the use of fluoxetine and abortion related significantly (OR=1.10, 95%=1.01-1.21), but also found that pregnant before the withdrawal of fluoxetine depression miscarriage risk also increased, suggesting that abortion may be related with depression itself, instead of drugs.
Three, early exposure to Pa Rossi Dean
Pa Rossi Dean has a clear association with congenital malformations and is rarely used during pregnancy. Many studies have found that prenatal exposure to paroxetine and increased risk of heart defects and congenital malformation, the evidence is sufficient. This also prompted FDA in 2005 issued a warning against the use of Pa Rossi Dean in early pregnancy, since then, the proportion of pregnant women in the use of has dropped from 19% in 2002-2006 to 2007-2010 in less than 0.1%.
Four, early pregnancy exposure to sertraline
Seculin is currently the most commonly used SSRIs during pregnancy in the United States, the proportion has increased from 16% in 2002-2006 to 2007-2010 in the year of 35%.
1 congenital malformation
Most studies suggest that sertraline risks caused by congenital malformation of the lower; few studies have found the defects related to respiratory system, absence, anal atresia, anencephaly, craniosynostosis etc..
Most of the studies are of the view that the use of sertraline in early pregnancy has no teratogenic risk potential, only draw the opposite results is a Danish Medical Research Association (n=817). In addition, based on two retrospective cohort study that different populations of early pregnancy using Seculin associated with respiratory defects; Sloan epidemiology of birth defects research shows that early pregnancy exposure associated with Seculin, baby absence, anal atresia congenital defects. The proportion of mothers who did not have a brain or cranial suture had a higher proportion of Seculin. The NBDPS study showed that, compared with the non deformed baby mother, anencephaly, Seculin cranial suture synostosis, omphalocele baby's mother in the exposure rate was significantly higher.
2 cardiovascular abnormalities
There are few studies on Seculin and congenital heart disease. The Danish record linkage study showed that prenatal exposure to sertraline can increase the overall risk of congenital heart defects, but many research results are not consistent, there is no conclusion.
Seculin has not been found to be associated with an increased risk of miscarriage in early pregnancy.
Five, late intrauterine exposure and neonatal complications
1 neonatal persistent pulmonary hypertension
Late SSRIs exposure can significantly increase the risk of PPHN. Persistent pulmonary hypertension (PPHN) is a rare disease of the heart with severe respiratory failure, with an incidence of about 10-20/100000. A large case control study in 2006 found that the risk of developing PPHN in pregnant women exposed to SSRIs in late pregnancy was 6 times higher. Therefore, the FDA issued a public health warning, suggesting that late pregnancy SSRIs treatment can increase the risk of neonatal PPHN. The Swedish population study and US cohort study found a significant correlation between the two (OR = 3.4 and 1.36, respectively). A large-scale international record linkage study also showed that the late pregnancy exposure to citalopram, fluoxetine, Pa Rossi Dean and Seculin can make a 2 fold increased risk of neonatal PPHN.
2, other neonatal adverse outcomes
Late SSRIs exposure can increase the risk of neonatal adaptation, premature birth, low birth weight, cesarean section, neonatal behavioral changes, Chiari I malformation, etc..
Late pregnancy exposure to SSRIs has been recognized as one of the risk factors for neonatal adjustment disorder. There are reports that delivery before taking SSRIs pregnant women, newborn respiratory distress, temperature instability, feeding difficulties, neuroticism, irritability, convulsions, rigidity, hypoglycemia, jaundice and other symptoms of neonatal adaptation disorder. These symptoms are associated with high dose drug therapy, especially Pa Rossi Dean. Sudden withdrawal after birth can lead to toxic effects associated with discontinuation of SSRI.
The use of SSRIs in late pregnancy was associated with an increased risk of preterm infants (37 weeks of gestation), a lower mean gestational age, lower birth weight, lower Apgar scores, higher cesarean section, and higher rates of neonatal ICU hospitalization. Other behavioral changes related to SSRIs exposure in late pregnancy include: increased locomotor activity, shivering, rapid eye movement sleep, and decreased response to pain.
Some studies have found that SSRIs treatment during pregnancy can affect the fetal nervous behavior, such as respiratory depression, increased locomotor activity. A recent study also found that children who were exposed to SSRIs during pregnancy had a significantly increased risk of developing Chiari I malformation.
During pregnancy should continue SSRIs treatment is still a controversial dilemma in the drug label risk of pregnancy and lactation will help explain the reasons of drug withdrawal in patients during pregnancy to the doctor. Every pregnant woman with depression should consult a doctor to weigh the pros and cons of disease treatment and medication risk
For pregnant women with mild to moderate depression, a gradual reduction in dose is appropriate and may be considered as a non pharmacological treatment. There are a variety of non drug treatment, can improve maternal depression and other mental disorders, such as cognitive and psychological treatment, Omega -3 fatty acid supplements, exercise, light therapy, etc.. In addition, under the premise of considering the disease, it should be recommended that women of childbearing age to avoid the use of SSRIs, instead of other forms of treatment.
However, SSRIs is recommended for women with recurrent and severe depression, and it has been proven to be the most effective treatment. The use of fluoxetine and Pa Rossi Dean should be avoided in the early stage of pregnancy, and the teratogenic risk is higher than that of other SSRIs. Due to the limited research, the use of SNRIs should also be cautious.
In short, the choice of treatment programs for pregnant women with depression should be based on personalization. From the point of view of public health, it is important to monitor the development of the fetus during the pregnancy and the whole childhood. The researchers suggest that early exposure to any SSRIs should be performed on a regular basis, and early detection and intervention of potential birth defects can be detected by ultrasound and fetal echocardiography.