Background No relationship has been reported between nonopiate neonatal abstinence syndrome (NAS) and anthropometric indices, including head circumference (HC). The purpose of this study was to determine the relationship between maternal nonopioid drug use and HC at birth in neonates with NAS. Methods This retrospective observational study included neonates born between January 1, 2010 and March 31, 2019, whose mothers had been taking antipsychotic, antidepressant, sedative, or anticonvulsant medications. The outcome measures were HCs of NAS infants and controls. Results Of 159 infants, 33 (21%) were diagnosed with NAS. There was no maternal opioid use among mothers during pregnancy. The HCs in the NAS group were significantly smaller than those in the control group. The median z-scores for HC at birth were −0.20 and 0.29 in the NAS group and the control group, respectively (P = .011). The median HCs at birth were 33.0 and 33.5 cm in the NAS group and the control group, respectively. Multivariate analysis revealed that maternal antipsychotic drug use and selective serotonin reuptake inhibitors were independently associated with NAS (P < .001 and P = .004, respectively). Notably, benzodiazepine use and smoking were not independent risk factors. Conclusions The results suggest an association between maternal antipsychotic drug use and NAS, which was further associated with decreased HC. Careful monitoring of maternal drug use should be considered to improve fetal outcomes.

BackgroundNeonatal abstinence syndrome (NAS) induced by opiate use is common worldwide. Psychiatric drugs are a more common cause of NAS in Japan but infants of mothers taking psychiatric medications do not always develop NAS. The purpose of this study was to develop a practical model for predicting the onset of nonopiate‐induced NAS, using variables available at birth.MethodsIn this diagnostic study, prediction models were developed using multivariable logistic regression with retrospective data collected at our hospital between 2010 and 2019. The NAS diagnosis was based on the Isobe score, and maternal medications were converted to dose equivalents.ResultsA total of 164 maternal and infant dyads met the inclusion criteria; 91 were included in the analysis, of whom 29 infants (32%) were diagnosed with NAS. Final models were created with and without the drug indices. The model without the drug indices consisted of neonatal head circumference in z‐scores and Apgar scores at 5 min < 9, and the model with the drug indices included these, as well as antipsychotics and hypnotics indices. The C‐statistics were 0.747 (95% CI: 0.638–0.856), and 0.795 (95% CI: 0.683–0.907), respectively, indicating that the models possessed good predictive accuracy for NAS onset.ConclusionsThis study developed models that predicted nonopiate‐induced NAS accurately. They may be further improved through the use of drug indices.

Histidine-rich glycoprotein (HRG) has been reported to inhibit signaling leading to the release of high mobility group box 1 protein, a damage-associated molecular pattern. The present study aimed to determine the longitudinal change in HRG levels in extremely preterm infants and assess whether complications such as bronchopulmonary dysplasia (BPD) were associated with differences in HRG levels. In this multicenter, prospective, observational study, we measured serum HRG levels every 2 weeks from birth to 8 weeks of age. Serum HRG was measured using an enzyme-linked immunosorbent assay. We included 19 extremely preterm infants in the study and 74 samples were analyzed. The median gestational age was 26.0 weeks, and the median birth weight was 858 g. Serum HRG levels showed a significant upward trend after birth (p < 0.001); median HRG concentrations at birth and at 2, 4, 6, and 8 weeks of age were 1.07, 1.11, 2.86, 6.05, and 7.49 µg/mL, respectively. Onset of BPD was not associated with differences in serum HRG levels. Further, the serum HRG levels increased significantly after birth in extremely preterm infants.