Poor neonatal adaptation syndrome: Toward a clinical consensus to guide research and counseling

Untreated or undertreated unipolar perinatal depression (PND) and anxiety are associated with myriad risks for both mother and infant. PND has been associated with adverse maternal outcomes including poor prenatal care, substance use, and suicide,1,2 adverse obstetric outcomes including preterm labor and birth, operative delivery, and preeclampsia,3,4 adverse neonatal outcomes including low birth weight and fetal distress,3,4 and abnormal infant/child development.5 Perinatal anxiety has similarly been associated with preterm birth, low birth weight, being small for gestational age, hypertensive disorders of pregnancy, and abnormal infant/child development57 as well as increased risk of postpartum depression and low breastfeeding rates.8 On the contrary, antenatal antidepressant use, which may be clinically indicated in moderate or severe PND and/ or anxiety, has been associated with small absolute risks of congenital malformation, obstetrical complications, and persistent pulmonary hypertension of the newborn and is more commonly associated with poor neonatal adaptation syndrome (PNAS).9,10 Studies evaluating potential risks of antenatal antidepressant use for mother and infant inherently have limitations as they are necessarily observational in design, limiting the quality of the evidence base. Further complicating the issue is the question of clinical relevance; not all statistically significant differences are clinically significant differences, and a critical part of categorizing risk is understanding the magnitude of individual contributory factors. Despite these limitations, clinicians must develop a personalized treatment plan, one that often balances suspected risks, known risks, and unknown risks of antenatal antidepressant use against under/untreated antenatal depression. To determine if antenatal antidepressant treatment is clinically indicated, clinicians should consider factors including current and past psychiatric disorder, symptom severity, suicide risk, current and past psychiatric treatment efficacy and tolerability, medical comorbidities, family psychiatric history, and patient treatment preference (including psychotherapies and other nonpharmacologic interventions). In addition to the clinician's careful assessment of the patient to determine a treatment plan, individual patients will assess the risks, benefits, and alternatives to antenatal antidepressant use differently according to their own priorities and values, which must be taken in consideration to produce an acceptable treatment plan for the patient. In the present issue of Acta Psychiatrica Scandinavica, Kautzky et al present a comprehensive updated systematic review and metaanalysis of studies including women and their infants with antenatal SSRI or SNRI exposure. Among antenatal depressed individuals, a clinically negligible but statistically significant decrease in gestational age as measured in weeks (mean difference = −0.47 [−0.74; −0.21]) in antidepressant exposed infants compared to healthy controls can be compared to clinically negligible but statistically significant decrease in gestational age found for unexposed infants of depressed mothers (mean difference = −0.36, [−0.81, 0.08]) compared to healthy controls. Increases in preterm birth were found in both comparisons between exposed infants and healthy controls (odds ratio = 1.75 [1.38; 2.21]) and between untreated and treated depressed individuals (odds ratio = 2.36 [1.35; 4.15]). Additionally, although a clinically negligible statistically significant increase in low birth weight was found in exposed infants (mean difference = −69.75 grams [−115.51, −23.99]) compared to healthy controls, no such difference was observed between exposed infants and unexposed infants of depressed mothers. Given their analyses, the authors suggest that differences in low birth weight and preterm birth may be largely driven by PND rather than antenatal antidepressant use. PNAS, also referred to as neonatal adaptation syndrome, is a potentially clinically relevant risk to antenatal antidepressant use, and Kautzky et al further categorize its phenomenology and risk.11 PNAS generally refers to an apparently selflimited syndrome of crying, jitteriness, lethargy, mild respiratory distress, hypothermia, hypoglycemia, sleep disturbances, abnormal muscle tone, tremor, and rarely seizures that lasts up to two weeks postbirth.12 The etiology remains unclear, although withdrawal and overstimulation of serotoninergic systems in the infant have alternately been proposed. Kautzky et al evaluated