Objective To determine the impact of maternal and fetal single nucleotide polymorphisms (SNPs) in key betamethasone (BMZ) pathways on neonatal outcomes. Study design DNA was obtained from women given BMZ and their infants. Samples were genotyped for 73 exploratory drug metabolism and glucocorticoid pathway SNPs. Clinical variables and neonatal outcomes were obtained. Logistic regression analysis using relevant clinical variables and genotypes to model for associations with neonatal respiratory distress syndrome (RDS) was performed. Results 109 women delivering 117 babies were analyzed. Sixty-four babies (49%) developed RDS. Multivariable analysis revealed that RDS was associated with maternal SNPs in CYP3A5 (OR 1.63, 95%CI 1.16–2.30) and the glucocorticoid receptor (OR 0.28, 95%CI0.08–0.95) and fetal SNPs in ADCY9 (OR 0.17, 95%CI 0.03–0.80) and CYP3A7*1E (rs28451617, OR 23.68, 95%CI 1.33–420.6). Conclusion Maternal and fetal genotypes are independently associated with neonatal RDS after treatment with BMZ for preterm labor.

CYP3A5 genotype plays a role in nifedipine concentration when used as a tocolytic.

OBJECTIVE We previously demonstrated that maternal and fetal genotypes are independently associated with neonatal respiratory distress syndrome (RDS). The objective of the current study is to determine the impact of maternal and fetal single nucleotide polymorphisms (SNPs) in key betamethasone (BMZ) pathways on respiratory outcomes that serve as markers for severity of disease. STUDY DESIGN DNA was obtained from women given BMZ and their infants. Samples were genotyped for 73 exploratory drug metabolism and glucocorticoid pathway SNPs. Clinical variables and neonatal outcomes were obtained. Logistic regression analysis controlling for relevant clinical variables to determine SNP impact on bronchopulmonary dysplasia (BPD), need for respiratory support, and surfactant therapy use was performed. RESULTS 109 women delivering 117 infants were analyzed. 14.5% of the infants developed BPD, 70.8% needed some respiratory support after birth, and 27.5% needed surfactant. In a multivariable regression analysis, gestational age at delivery was associated with most neonatal respiratory outcomes (p≤0.01) and chorioamnionitis was associated with BPD (p<0.03). Genotypes associated with respiratory severity outcomes were as follows: BPD- Fetal IPO13 (rs4448553; OR 0.01, 95% CI 0.00–0.92); Surfactant use- Maternal IPO13 (rs2428953 and 2486014; OR 13.8, 95%CI 1.80–105.5 and OR 35.5, 95% CI 1.71–736.6, respectively). CONCLUSIONS Several discrete maternal and fetal SNPs in the Importin 13 gene (IPO13) may be associated with neonatal respiratory outcomes after maternal antenatal corticosteroid treatment for anticipated preterm birth.

IMPORTANCEHypertensive disorders of pregnancy are associated with future cardiovascular disease, perhaps because of subclinical cardiac dysfunction before pregnancy leading to impaired adaptation to pregnancy. Natriuretic peptides are promising biomarkers for detecting subclinical cardiac dysfunction outside of pregnancy.OBJECTIVE To investigate whether higher concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) in early pregnancy would be associated with hypertensive disorders of pregnancy and hypertension 2 to 7 years post partum. DESIGN, SETTING, AND PARTICIPANTSThis cohort study used data from the The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be Heart Health Study, a prospective multicenter observational study. A total of 4103 nulliparous women with complete data and no prepregnancy hypertension or diabetes who were treated at 8 clinical sites were included. Women were followed up with for 2 to 7 years after pregnancy. Data were collected from October 2010 to October 2017, and data were analyzed from August 2020 to November 2021.EXPOSURES NT-proBNP concentration, measured using an electrochemiluminescence immunoassay from a first-trimester blood sample. MAIN OUTCOMES AND MEASURESHypertensive disorders of pregnancy and incident hypertension (systolic blood pressure of 130 mm Hg or diastolic blood pressure of 80 mm Hg or use of antihypertensive agents) at follow-up visit.RESULTS A total of 4103 women met inclusion criteria; the mean (SD) age was 27.0 (5.6) years. Among these women, 909 (22.2%) had an adverse pregnancy outcome, and 817 (19.9%) had hypertension at the follow-up visit. Higher NT-proBNP concentrations were associated with a lower risk of hypertensive disorders of pregnancy (adjusted odds ratio per doubling, 0.81; 95% CI, 0.73-0.91), which persisted after adjustment for age, self-reported race and ethnicity, early-pregnancy body mass index, smoking, and aspirin use. Similarly, higher NT-proBNP concentration in early pregnancy was also associated with a lower risk of incident hypertension 2 to 7 years after delivery (adjusted odds ratio per doubling, 0.84; 95% CI, 0.77-0.93), an association that persisted after controlling for confounders, including hypertensive disorders of pregnancy. CONCLUSIONS AND RELEVANCEIn this cohort study, higher NT-proBNP concentrations in early pregnancy were associated with a lower risk of hypertensive disorders of pregnancy and hypertension 2 to 7 years post partum. These findings suggest that normal early-pregnancy cardiovascular physiology, as assessed by NT-proBNP concentration, may provide biologic insights into both pregnancy outcome and cardiovascular disease risk.

BackgroundNausea and vomiting of pregnancy (NVP) is a common condition. The objective of this study was to evaluate the association between response to antiemetics in the treatment of NVP and genetic polymorphisms in the serotonin receptor subunit genes HTR3A and HTR3B.MethodsPregnant women ≥18 years of age with NVP starting antiemetic therapy with promethazine, prochlorperazine, metoclopramide, or ondansetron at ≤ 16 weeks gestational age were eligible. The study recruited 29 women with complete data and sampling who returned for their one week follow-up and were genotyped for HTR3A and HTR3B polymorphisms. Severity of NVP was captured (using Pregnancy Unique Quantification of Emesis (PUQE) and Quality of Life (QOL) tools) upon enrollment and after one week of antiemetic therapy. These measures were correlated with pharmacogenetic variability.ResultsSubjects with genotype associated with high serotonin affinity of the 5-HT3B receptor (rs1176744, CC) required more antiemetic medications (p < 0.001) than other subjects. Those with genotypes associated with increased expression of the 5-HT3A receptor subunit (rs1062613, CT or TT) had worse final PUQE scores (p = 0.01) than other subjects while rs3782025 variants carriers had significantly better initial (p = 0.02) and final (p = 0.02) PUQE scores than other subjects.ConclusionsHTR3B and HTR3A gene variants may contribute to variability in response to antiemetic therapy for NVP.