Lopinavir-Ritonavir Impairs Adrenal Function in Infants

Background Perinatal treatment with lopinavir boosted by ritonavir (LPV/r) is associated with steroidogenic abnormalities. Long-term effects in infants have not been studied. Methods Adrenal-hormone profiles were compared at weeks 6 and 26 between human immunodeficiency virus (HIV)-1–exposed but uninfected infants randomly assigned at 7 days of life to prophylaxis with LPV/r or lamivudine (3TC) to prevent transmission during breastfeeding. LPV/r in vitro effect on steroidogenesis was assessed in H295R cells. Results At week 6, 159 frozen plasma samples from Burkina Faso and South Africa were assessed (LPV/r group: n = 92; 3TC group: n = 67) and at week 26, 95 samples from Burkina Faso (LPV/r group: n = 47; 3TC group: n = 48). At week 6, LPV/r-treated infants had a higher median dehydroepiandrosterone (DHEA) level than infants from the 3TC arm: 3.91 versus 1.48 ng/mL (P < .001). Higher DHEA levels (>5 ng/mL) at week 6 were associated with higher 17-OH-pregnenolone (7.78 vs 3.71 ng/mL, P = .0004) and lower testosterone (0.05 vs 1.34 ng/mL, P = .009) levels in LPV/r-exposed children. There was a significant correlation between the DHEA and LPV/r AUC levels (ρ = 0.40, P = .019) and Ctrough (ρ = 0.40, P = .017). At week 26, DHEA levels remained higher in the LPV/r arm: 0.45 versus 0.13 ng/mL (P = .002). Lopinavir, but not ritonavir, inhibited CYP17A1 and CYP21A2 activity in H295R cells. Conclusions Lopinavir was associated with dose-dependent adrenal dysfunction in infants. The impact of long-term exposure and potential clinical consequences require evaluation. Clinical Trials Registration NCT00640263

DOZ047.27: Esophageal atresia and polyhydramnios

Background Prenatal diagnosis of esophageal atresia (EA) is difficult and the detection rate is only 20–35%. Ultrasound features of EA are nonspecific with polyhydramnios as the most reported finding. Polyhydramnios is reported in approximately 2% of all pregnancies and thus have low specificity. The aim of our retrospective study is to explore perinatal characteristics of EA patients with prenatal suspicion of EA. Methods Patients with EA born in the periods 1996–2002 and 2011–2017 were included after consent of the parents. Data regarding the pregnancy, birth, and perinatal treatment were obtained from medical records. Results We registered a total of 124 EA patients: 68 from 1996 to 2002, and 56 from 2011 to 2017. Among the 124 patients, 5(4%) had type Gross A or B, 108(87%) type C, 6(5%) type D, and 5(4%) type E. 73(59%) patients had an associated anomaly. 20/124(16%) patients had a prenatal suspicion of EA, and there were no significant differences between neonates with and without prenatal suspicion of EA in terms of birth weight, gestational age, and prematurity. Patients with prenatal suspicion of EA had more caesarean sections, were more frequently born at regional hospitals, and had more associated anomalies. Polyhydramnios was registered in 70 patients; in 18 of these (90% of all with prenatal diagnosis) a prenatal suspicion of EA had been raised. In 52 EA patients with polyhydramnios, no prenatal statement about anomaly was registered. Four of 5 patients (90%) with type A and B had a prenatal suspicion of EA. Corresponding number for type C was 15/108(14%) and 1/5(20%) with type E. Conclusion The detection rate for EA is low, and prenatal suspicion of EA implicates a more serious condition with higher morbidity than EA patients born without prenatal suspicion of malformation. Four of five patients without fistula to lower esophagus (type A and B) had a prenatal suspicion of EA, and polyhydramnios is the ‘signal sign’ for the possible presence of esophageal atresia.

Mechanisms of HIV Transmission

HIV is a sexually transmitted infection. Most new HIV infections in the United States are the result of sex, but it is rare for HIV to be transmitted through oral sex. The risk of HIV transmission to a receptive partner remains higher than that to an insertive one; however, both are at risk. Anything that compromises the integrity of mucous membranes, such as sexually transmitted infections, may increase the risk of transmission. Although not 100% effective, keeping an infected partner’s viral load low reduces the risk of transmission to an HIV-negative partner. Maternal transmission is a larger concern in developing countries due to lack of access to perinatal treatment with antiretroviral drugs.

Intrauterine Surgery for Spinal Defects: What is the Role of Ultrasound?

ABSTRACT Ultrasound imaging has led to the diagnosis of fetal anomalies that can affect many organ systems. Since the development of high-resolution real-time ultrasound, the possibility of surgical intervention before birth to correct or treat prenatally diagnosed abnormalities has been realized. Fetal surgery has become a new standard of care for the perinatal treatment of myelomeningocele for mothers and fetuses that meet the specific criteria. In this review, we will consider the role of ultrasound for open fetal surgery or minimally invasive fetal surgery approaches. How to cite this article Moreira de Sá RA, Peixoto-Filho F, Cima L. Intrauterine Surgery for Spinal Defects: What is the Role of Ultrasound? Donald School J Ultrasound Obstet Gynecol 2016;10(3):297-300.

Expression of 5HT-related genes after perinatal treatment with 5HT agonists

Serotonin (5HT) is a biologically active amine with diverse roles in the mammalian organism. Developmental alterations in 5HT homeostasis could lead to exposure of the developing brain to non-optimal serotonin concentrations that may result in developmental and behavioral deficits. In order to explore the molecular basis of the effects of developmental disturbances on 5HT metabolism on adult central 5HT homeostasis, observed in our previous studies, we measured changes in gene expression of the neuronal 5HT-regulating proteins in adult animals after perinatal treatment with the immediate 5HT precursor 5-hydroxytryptophan (5HTP, 25 mg/kg), or monoamine oxidase (MAO) inhibitor tranylcypromine (TCP 2 mg/kg), during the period of the most intensive development of 5HT neurons — from gestational day 12 until postnatal day 21. Adult animals were sacrificed and the relative mRNA levels for tryptophan hydroxylase 2, MAO A, MAO B, receptors 5HT1A and 5HT2A, 5HT transporter (5HTT) and vesicular monoamine transporter (VMAT) were determined in the raphe nuclei region and prefrontal cortex using Real-Time Relative qRT-PCR. In comparison to the saline treated animals, treatment with 5HTP caused mild but significant increase in MAO A and MAO B mRNA abundance. TCP-treated animals, besides an increase in mRNA abundance for both MAO genes, displayed significantly increased 5HTT and VMAT2 mRNA levels and significantly decreased 5HT1A receptor mRNA levels. Our results suggest that perinatal exposure of rats to 5HTP, and especially TCP, induces long-lasting/permanent changes in the expression of 5HT-regulating genes, that presumably underlie 5HT-related neurochemical and behavioral changes in adult animals.

Soluble epoxide hydrolase in the generation and maintenance of high blood pressure in spontaneously hypertensive rats

We hypothesized that perinatal inhibition of soluble epoxide hydrolase (SEH), which metabolizes epoxyeicosatrienoic acids in the arachidonic acid (AA) cascade, with an orally active SEH inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), would persistently reduce blood pressure (BP) in adult SHR despite discontinuation of AUDA at 4 wk of age. Renal cytoplasmic epoxide hydrolase-2 (Ephx2) gene expression was enhanced in SHR vs. WKY from 2 days to 24 wk. Effects of perinatal treatment with AUDA, supplied to SHR dams until 4 wk after birth, on BP in female and male offspring and renal oxylipin metabolome in female offspring were observed and contrasted to female SHR for direct effects of AUDA (8–12 wk). Briefly, inhibition of SEH was effective in persistently reducing BP in female SHR when applied during the perinatal phase. This was accompanied by marked increases in major renal AA epoxides and decreases in renal lipoxygenase products of AA. Early inhibition of SEH induced a delayed increase in renal 5-HETE at 24 wk, in contrast to a decrease at 2 wk. Inhibition of SEH in female SHR from 8 to 12 wk did not reduce BP but caused profound decreases in renal 15( S)-HETrE, LTB4, TBX2, 5-HETE, and 20-HETE and increases in TriHOMEs. In male SHR, BP reduction after perinatal AUDA was transient. Thus, Ephx2 transcription and SEH activity in early life may initiate mechanisms that eventually contribute to high BP in adult female SHR. However, programmed BP-lowering effects of perinatal SEH inhibition in female SHR cannot be simply explained by persistent reduction in renal SEH activity but rather by more complex and temporally dynamic interactions between the renal SEH, lipoxygenase, and cyclooxygenase pathways.