Animal studies have failed to reveal evidence of teratogenicity; however, there was evidence of delayed ossification and effects on reproduction attributed to maternal toxicity. Decreased neonatal survival following maternal administration at exposures similar to or slightly greater than the maximum recommended human dose of 200 mg was also observed; the clinical significance is unknown. There are no controlled data in human pregnancy.

The results of several studies suggest that the use of SSRIs in the first trimester of pregnancy may be associated with an increased risk of cardiovascular and/or other congenital malformations; however, this association has not been clearly established. The association appears to be strongest for another SSRI, paroxetine.

Use of sertraline during pregnancy has been reported to cause symptoms compatible with withdrawal reactions in neonates whose mothers had taken sertraline. Neonates exposed to SSRIs and SNRIs late in the third trimester have uncommonly reported clinical findings including respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These effects have mostly occurred either at birth or within a few days of birth. These features are consistent with either a direct toxic effect of SSRIs and SNRIs, or possibly a drug discontinuation syndrome; in some cases, the clinical picture is consistent with serotonin syndrome. The results of a cohort study indicate that 30% of neonates who had prolonged exposure to SSRIs in utero experience symptoms, in a dose-response manner, of a neonatal abstinence syndrome after birth. The authors suggest that infants exposed to SSRIs should be closely monitored for a minimum of 48 hours after birth.

Epidemiological data have suggested that the use of SSRIs, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn. Data are not available for SNRIs.

One study compared 267 women exposed to an SSRI - either fluvoxamine, paroxetine, or sertraline, to 267 controls. Exposure to SSRIs was not associated with either increased risk for major malformations, higher rates of miscarriage, stillbirth, or prematurity. Mean birth weights among SSRI users were similar to controls as were the gestational ages. The study concluded that the SSRIs fluvoxamine, paroxetine, and sertraline did not appear to increase teratogenic risk when used in their recommended doses.

Animal data with sertraline have not shown an effect on fertility. Human case reports from some SSRIs have shown an effect on sperm quality that is reversible. As yet, the impact of this on human fertility has not been observed.

To monitor maternal-fetal outcomes of pregnant women exposed to antidepressant therapy, a National Pregnancy Registry for Antidepressants has been established. Healthcare providers are encouraged to prospectively register patients. For additional information: https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/

AU TGA pregnancy category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

This drug should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus, taking into account the risks of untreated depression.
-Oral concentrate and solution formulations containing alcohol: Not recommended.

AU TGA pregnancy category: C
US FDA pregnancy category: Not assigned.

Risk summary: Malformative risk is unlikely when given during the first trimester. There is inconclusive data on use of this drug in the third trimester to inform of a drug-related risk.

Comments:
-A pregnancy exposure registry is available.
-Neonates exposed to this drug late in the third trimester may require respiratory support, tube feeding, and/or prolonged hospitalization.
-Exposed neonates should be monitored after delivery for direct toxic effects of this drug, drug discontinuation syndrome, and serotonin syndrome (e.g., respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypo/hypertonia, hyperreflexia, tremor, jitteriness, irritability, constant crying).

See references

Use is not recommended; benefit to the mother should outweigh risk to the infant.

Excreted into human milk: Yes

Comments:
-This drug has been considered one of the preferred antidepressants during breastfeeding.
-Accumulation of the drug may occur in preterm infants with impaired metabolic activity; effects similar to neonatal abstinence may rarely present in these infants.
-Mothers taking an SSRI during pregnancy and postpartum may have difficulty breastfeeding and may require additional breastfeeding support.

Benign neonatal sleep myoclonus in a 4-month-old infant and agitation in that spontaneously resolved in another infant was reported to the Australian Adverse Drug Reaction Advisory Committee and may be related to the presence of sertraline in breastmilk.

Levels of sertraline in breastmilk are reported to be low; the weakly active metabolite desmethylsertraline may be detectable in low levels. In a study of 26 breastfeeding women who were, on average, 15.8 weeks postpartum and receiving an average of 124 mg sertraline daily for at least 14 days for severe depression, complete sets of milk sample data were available for 15 mothers. Analysis of these samples led the study authors to estimate that an exclusively breastfed infant would receive an average of 0.54% of the maternal weight-adjusted dosage. Pumping and discarding milk 8 to 9 hours after the mother's dose would decrease the infant's daily dosage by 17%.

Amounts of sertraline ingested by breastfed infants are reported to be small. There was an analysis of 30 breastfed infants aged 6 to 13 weeks, of which 19 were exclusively breastfed and 11 breastfed at least half the time. Serum sertraline levels were below 1 mcg/L in 22 infants. The other 8 infants had an average serum sertraline level of 7.9 mcg/L; their mothers were taking a average of 109 mg sertraline daily, with an average serum level of 52.8 mcg/L.

The data from one study on three breast-fed infants suggested that sertraline and/or its almost inactive metabolite norsertraline may be present at very low concentrations in the plasma of breast-fed infants. No adverse effects were noted in the infants.

A pooled analysis of 53 mother-infant pairs from published and unpublished cases found that infants had an average of 2% of the sertraline plasma levels of the mothers'; three of the infants had a plasma level greater than 10% of the mothers'.

A study of fourteen mother-infant pairs reported that while mothers receiving clinical doses of sertraline experienced substantial blockade of the platelet 5-HT transporter, platelet 5-HT uptake in nursing infants of treated mothers was unaltered.

Another study of twelve breast-feeding mothers reported that both sertraline and desmethylsertraline were present in all breast milk samples. Detectable levels of sertraline were reported in three nursing infants and detectable levels of desmethylsertraline were reported in six infants.

A case study of a mother breast-feeding while receiving sertraline therapy has also been reported. The drug was found to be present in the mother's milk. However, no sertraline was detected in the infant's serum and no abnormal occurrences were noted in the development of this infant either.

See references