Opportunities for probiotics and polyunsaturated fatty acids to improve metabolic health of overweight pregnant women.

Overweight during pregnancy predisposes both the mother and foetus to health complications. Maternal complications include gestational diabetes, obstetric problems and type 2 diabetes later in life. Complications for the offspring are not only restricted to the foetal period or birth, such as prematurity and foetal macrosomia, but may also have long-term metabolic health implications through the mechanism of early nutrition programming. One of the key metabolic components characterising overweight in the non-pregnant state is low-grade inflammation manifested by elevated levels of circulatory pro-inflammatory cytokines. In pregnancy, in addition to adipose tissue and placenta, inflammatory response may originate from the gut. The extent to which overweight induces metabolic maladaptation during pregnancy and further compromises maternal and child health is currently poorly understood. In this review, we evaluate recent scientific literature and describe the suggested links between overweight, gut and low-grade inflammation associated metabolic disorders. We focus on overweight pregnant women and gestational diabetes, and discuss how specific dietary factors, probiotics and long-chain polyunsaturated fatty acids (fish oil), might confer health benefits in combatting against metabolic risk factors.

Metformin vs. insulin in gestational diabetes. A randomized study characterizing metformin patients needing additional insulin.

AIMS: We compared metformin with insulin as treatment of gestational diabetes mellitus (GDM). Furthermore, we aimed to characterize metformin-treated patients needing additional insulin to achieve prespecified glucose targets. METHODS: We conducted a single centre randomized controlled study with non-inferiority design comparing metformin and insulin in the treatment of 217 GDM patients having birth weight as primary outcome variable. RESULTS: There were no significant differences in mean birth weight expressed in grams [+15 (90% confidence interval (CI): -121 to 89)] or SD units [+0.04 (90% CI: -0.27 to 0.18)] between the metformin and insulin groups. There were no significant differences in neonatal or maternal data between the groups. Only 23 (20.9%) of the 110 patients in the metformin group needed additional insulin. Compared with the patients on metformin only, those needing additional insulin were older (p = 0.04), their oral glucose tolerance test had been performed earlier and diabetes therapy started earlier in gestation (p = 0.01 and p = 0.004, respectively). The risk for additional insulin was 4.6-fold in women with baseline serum fructosamine concentration above median compared with those below median. CONCLUSIONS: Metformin is an effective alternative to insulin in the treatment of GDM patients. Serum fructosamine may help in predicting the adequacy of metformin treatment alone.

Maternal midtrimester free beta-HCG and AFP serum levels in spontaneous singleton pregnancies complicated by gestational diabetes mellitus, pregnancy-induced hypertension or obstetric cholestasis.

OBJECTIVES: The present study aims at finding out whether a connection exists between altered serum free beta-hCG and/or alpha-fetoprotein (AFP) levels and the manifestation of specific pregnancy complications [i.e. gestational diabetes mellitus (GDM), pregnancy induced hypertension (PIH) or intrahepatic cholestasis of pregnancy (ICP)]. METHODS: We compared free beta-hCG and AFP multiples of median (MoM) values in singleton pregnancies. The study population consisted of 117 pregnancies with GDM, 107 with PIH and 24 with ICP. The control group consisted of 1148 singleton pregnancies without any pregnancy complications. All were spontaneously conceived. RESULTS: In the group with GDM, both the free beta-hCG (0.72 MoM) and AFP MoM values (0.93) were significantly lower than in controls (beta-hCG 0.97 MoM, p = 0.0063 and AFP 1.01 MoM, p = 0.01). No statistically significant differences in the marker levels were observed between the ICP pregnancies and the control group. CONCLUSIONS: GDM has an impact on maternal midtrimester free beta-hCG and AFP levels and may change the DS screening result.

Postnatal adaptation after Caesarean section or vaginal delivery, studied with the static-charge-sensitive bed.

AIM: To compare postnatal adaptation between Caesarean and vaginal deliveries, by studying sleep states, oxygenation, heart rate and body movements. Another aim was to follow the adaptation of healthy, term, vaginally born babies. METHODS: Ten vaginally born and 12 neonates born by elective Caesarean section were recorded with a movement sensor (SCSB, static-charge-sensitive bed), electrocardiogram and oximeter. The recordings started 1.5 h after birth and lasted for 12 h. For the vaginal group, another 12 h recording was performed during the third night postpartum. RESULTS: Delivery mode did not affect sleep state distribution. The vaginal group had more oxyhaemoglobin desaturation episodes <95% than the Caesarean section group (mean +/- SD: 59 +/- 10% vs 42 +/- 22% of epochs, p = 0.03), especially in active sleep, but baseline saturation was similar (96 +/- 1% vs 95 +/- 3%, p = 0.93). The vaginal group had fewer movements during sleep than the Caesarean section group (movements of 5-10 s: 5 +/- 1 h(-1) vs 10 +/- 3 h(-1), p = 0.0001). During the first 3 d, the amount of sleeping and active sleep increased, whereas wakefulness and quiet sleep decreased. Baseline oxyhaemoglobin saturation and the number of movements of over 5 s increased. CONCLUSION: Delivery mode did not affect sleep state distribution but, unexpectedly, the vaginal group had more oxyhaemoglobin desaturation events and fewer body movements than the Caesarean section group. These differences during the first postnatal day remain unexplained, but they may reflect stress and pain during labour. After a few days, changes in sleep organization, and increases in oxyhaemoglobin saturation and frequency of body movements were noted in the vaginal group, which may represent recovery and adaptation to extrauterine life.

Comparison of the effects of antenatal magnesium sulphate and ritodrine exposure on circulatory adaptation in preterm infants.

We examined the effects of maternal magnesium sulphate (MgSO4) and ritodrine treatments on the autonomic cardiovascular control in preterm neonates with respiratory distress syndrome during the first 2 days of life. Serial measurements of heart rate (HR), blood pressure (BP) and respirogram were performed during the first 2 days of life in 28 preterm infants below 33 weeks of gestation with antenatal exposure to MgSO4 (n = 13) or ritodrine (n = 15), and in 12 nonexposed preterm controls. Spectral analysis was used for the quantification of HR and BP variability. Although antenatal MgSO4 exposure had no effect on HR or the systolic, diastolic or mean BP, it was associated with significant decreased beat-to-beat changes in BP. In contrast, ritodrine exposure had no consistent effects on the autonomic cardiovascular control during the first 2 days of life. Our data suggest that maternal MgSO4 treatment decreases the neonatal high frequency changes in BP. This early vascular stabilizing effect of antenatal MgSO4 exposure may contribute to a lowered risk of cerebral vascular catastrophes, in the vulnerable areas of the brain, among the preterm infants with respiratory distress syndrome.

Serum free beta-HCG and alpha-fetoprotein levels in IVF, ICSI and frozen embryo transfer pregnancies in maternal mid-trimester serum screening for Down's syndrome.

BACKGROUND: The aim of this study was to compare the maternal mid-trimester free beta-HCG and alpha-fetoprotein (AFP) levels in pregnancies conceived by assisted reproduction technology and spontaneous pregnancies in Down's syndrome screening. The influence of the number of embryos transferred and the amount of gonadotrophins used on the marker levels was also evaluated. METHODS: The study population consisted of 58 IVF, 32 ICSI and 26 frozen embryo transfer (FET) singleton pregnancies. The levels of beta-HCG and AFP were compared with the control group of 6548 singleton spontaneous pregnancies. RESULTS: The false positive rate (FPR) in the Down's syndrome screening was 19% overall in assisted reproductive technology pregnancies, being highest (30.8%) in the FET group. The free beta-HCG multiples of the median (MoM) values were statistically significantly elevated only in the FET group (1.33 MoM; P = 0.012). A positive correlation between the number of embryos transferred and the marker levels was observed in the IVF group. No correlation was found between the amount of gonadotrophin medication used and the marker levels. CONCLUSIONS: The present data confirm that the overall FPR in the serum screening for Down's syndrome in assisted reproduction pregnancies is high, resulting in unnecessary invasive procedures.

Maternal magnesium sulfate treatment is associated with reduced brain-blood flow perfusion in preterm infants.

OBJECTIVE: To examine the influence of antenatally administered magnesium sulfate (MgSO4) and ritodrine on cerebral blood flow and systemic hemodynamics in preterm infants. DESIGN: Prospective, observational study. SETTING: Neonatal intensive care unit of a university central hospital. PATIENTS: Fifty-five preterm infants age <33 wks of gestation. INTERVENTIONS: Serial Doppler examinations of the brain circulation, heart rate, systemic blood pressure, and echocardiographic assessment of ductus arteriosus shunting were performed during the first week of life in infants exposed antenatally to maternal MgSO4 (n = 19) or ritodrine treatment (n = 17), and in 19 nonexposed preterm controls. MEASUREMENTS AND MAIN RESULTS: Cerebral blood flow velocity measurements were obtained from the anterior cerebral artery and internal carotid artery. Perfusion pressure and indices of resistance and blood flow in both vessels were subsequently derived. Maternal MgSO4 had no effect on neonatal cerebral blood flow velocity or resistance, but was associated with decreased (p <.05) perfusion pressure and blood flow in the anterior cerebral artery and internal carotid artery during the first day of life. Systolic blood pressure and pulse pressure were also lower (p <.05) during the whole study period in the MgSO4-exposed infants when compared with the controls. Maternal ritodrine treatment, on the other hand, had no consistent effects on either neonatal cerebral or systemic hemodynamics. CONCLUSIONS: Our data indicate that maternal MgSO4 treatment, in contrast to antenatal ritodrine, is associated with lowered cerebral perfusion in preterm infants on the first day of life.

Antenatal magnesium sulphate exposure is associated with prolonged parathyroid hormone suppression in preterm neonates.

UNLABELLED: The effects of maternal magnesium sulphate treatment on neonatal mineral status and parathyroid hormone secretory response were studied in 8 exposed and 27 control preterm infants during the first 2 wk of life. Antenatal magnesium sulphate resulted in hypermagnesaemia during the first 3-7 d of life without affecting other serum mineral concentrations. CONCLUSION: Early hypermagnesaemia was associated with hypercalciuria during the first 3 d and parathyroid hormone suppression up to the age of 2 wk in the exposed infants.

Transplacental transfer of amitriptyline and nortriptyline in isolated perfused human placenta.

RATIONALE: Although tricyclic antidepressants (TCAs) have gained wide acceptance for use in the treatment of depression in pregnant women, their pharmacokinetics during pregnancy have been poorly characterized. The aim of the present study was to investigate the transplacental transfer of amitriptyline (AMI) and its main active metabolite nortriptyline (NOR) in isolated perfused human placenta. METHODS: Nine term human placentae were obtained immediately after delivery with maternal consent and a 2-h non-recirculating perfusion of a single placental cotyledon was performed. AMI (200 ng/ml) and NOR (150 ng/ml), with antipyrine as a reference compound, were added to the maternal reservoir and their appearance to the fetal circulation was followed for 2 h. AMI and NOR concentrations were measured by high performance liquid chromatography (HPLC) and antipyrine concentrations spectrophotometrically. RESULTS: The mean (SD) transplacental transfers (TPT(SS)%) for AMI and NOR were 8.2 (2.3)% and 6.5 (1.8)%, respectively, calculated as the ratio between the steady-state concentrations in fetal venous and maternal arterial sides. The TPTs of AMI and NOR were 81% and 62% of the freely diffusable antipyrine. The absolute fraction of the dose that crossed the placenta (TPT(A)) was moderately, but significantly higher for AMI (7.7%) than for NOR (5.7%) (P=0.037). In all perfusions, steady state at the fetal side was reached by 30 min for AMI and by 50 min for NOR in the fetal side. The viability of the placentae was retained during the 2-h perfusion, as evidenced by unchanged pH of the perfusate and by stable perfusion pressures in fetal artery and stable antipyrine transfer. CONCLUSIONS: Both AMI and NOR cross the human placenta. However, the fetal exposure with NOR may be somewhat smaller compared with AMI, probably due to the higher lipophilicity of AMI.

Periodic spectral components of fetal heart rate variability reflect the changes in cord arterial base deficit values: a preliminary report.

Fetal distress changes the function of the autonomic nervous system. These changes are reflected in the fetal heart rate and can be quantified with power spectrum analysis of heart rate variability. The purpose of this study was to find out whether spectral components of fetal heart rate variability (FHRV) during labor are associated with fetal cord arterial base deficit values at birth. The association between FHRV and umbilical cord arterial base deficit was studied in 14 singleton fetuses with normal pregnancy at 35-40 weeks of gestation. Fetal ECG was recorded by scalp-electrode using a STAN Fetal ECG monitor (Cinventa Ab, Mölndal, Sweden). FHRV was quantified by computing Fast-Fourier-transformed heart rate (HR) spectra at three frequency bands: low-frequency (LF) 0.03-0.07 Hz, mid-frequency (MF) 0.07-0.13 Hz and high-frequency (HF) 0.13-1.0 Hz. We found that total FHRV and MF FHRV were lower in fetuses with cord arterial base deficit 8 to 12 mmol/L in comparison to the fetuses with normal cord arterial base deficit value (P=0.02 and P=0.01, respectively). A linear correlation was found between the spectral densities and the cord arterial base deficit values (r=0.4 and r=0.6, respectively). We conclude that the results suggest changes in the autonomic nervous cardiac control in fetuses with cord arterial base deficit between 8 to 12 mmol/L. The clinical applicability of our observations on FHRV in predicting fetal distress remains to be further studied.

Fetal oxygen saturation during epidural and paracervical analgesia.

BACKGROUND: We wanted to assess changes in fetal oxygenation during maternal epidural or paracervical analgesia in labor. METHODS: A prospective, open and non-randomized study. Twenty healthy parturients were enrolled before they asked for pain relief. Informed consent was obtained. Fetal and maternal oxygen saturations were measured before and up to 1 h after the initiation of analgesia. Fetal oximetry was performed with the Nellcor N-400 oximeter+FS-14B fetal oxygen sensor (Nellcor Puritan Bennett, Pleasanton, California, USA). Maternal oximetry was done with Datex Satlite portable monitor (Datex, Finland). Visual analog scale was used for assessing pain relief. Two-way analysis of variance and students t-test were used for statistical analyses. RESULTS: Fetal oxygenation initially improved in both groups. The saturation then returned to baseline in both groups. In the epidural group, the values remained at baseline or slightly below, while in the paracervical group the saturation remained a little higher than baseline (p=0.009). No change was seen in maternal oxygenation or heart rate. No change in fetal heart rate was found either. Epidural block was superior to paracervical block with respect to pain relief (p=0.002). CONCLUSIONS: There was a small but significant difference in fetal oxygenation between epidural and paracervical groups during the observation period. The magnitude of the difference is hardly clinically significant. A larger, randomized study is needed to elucidate the mechanisms behind this finding.

The transplacental transfer of the macrolide antibiotics erythromycin, roxithromycin and azithromycin.

OBJECTIVE: To investigate the transplacental transfer of the macrolide antibiotics erythromycin, roxithromycin and azithromycin. METHODS: Twenty-one term placentas were obtained with maternal consent immediately after delivery and a two-hour nonrecirculating perfusion of a single placental cotyledon was performed. Erythromycin (2 microg/mL), roxithromycin (2 microg/mL) and azithromycin (0.3 microg/mL) were infused to the maternal inflow at a constant rate, with antipyrine as a reference compound, and their appearance in the fetal circulation was followed. Drug concentrations were measured by high performance liquid chromatography for 120 min. RESULTS: The mean transplacental transfers (TPT(SS)) for erythromycin, roxithromycin and azithromycin were 3.0%, 4.3% and 2.6%, respectively, calculated as the ratio between the steady state concentrations in fetal venous and maternal arterial sides. Similar results were obtained when the TPT was calculated as the absolute amount of drug transferred across the placenta during 2-hour perfusion (TPT(A)). No significant differences were found among the three macrolides in TPT(SS) (P = 0.39) or TPT(A) (P = 0.35). The TPT(SS) of erythromycin, roxithromycin and azithromycin were 41%, 35% and 32% of the freely diffusable reference compound antipyrine, respectively. Steady state was reached in 60 minutes in each perfusion indicating sufficient perfusion time. CONCLUSION: The limited transplacental transfer of erythromycin, roxithromycin and azithromycin suggests compromised efficacy in the treatment of fetal infections. On the other hand, the placenta seems to produce an effective barrier reducing the fetal exposure when these three macrolides are used to treat maternal infections.

Maternal midtrimester serum AFP and free beta-hCG levels in in vitro fertilization twin pregnancies.

We aimed to compare the levels of alpha-fetoprotein (AFP) and free beta-human chorionic gonadotrophin (beta-hCG) levels as multiples of the median (MoM) values between spontaneous and in vitro fertilized (IVF) twin pregnancies. The control group of spontaneous singleton pregnancies was used for calculating the gestational age specific median levels of the values. Within a cohort of 19 310 pregnancies, 145 twin pregnancies were identified. The data were collected from Down syndrome (DS) screening programmes in four University catchment areas in Finland between 1994-98. Maternal midtrimester serum marker levels were measured across gestational weeks 14-18. There were no fetal chromosome anomalies in either of the twin groups or the singleton group. Serum AFP of 145 and beta-hCG values of 39 spontaneous twin pregnancies were compared to the values of 6548 singleton pregnancies. In IVF twins 30 AFP and 29 beta-hCG values were compared to the levels of the control group. Both AFP and beta-hCG values were twice as high in the spontaneous twin pregnancies (medians 2.18 and 1.83 MoM respectively) as in the singleton group (medians 1.00 and 1.00 MoM respectively). In IVF twin pregnancies beta-hCG levels were higher (median 2.20 MoM) than in spontaneous twins (p=0.08), whereas no significant difference was found in AFP levels (2.30 MoM). In conclusion, the higher levels of beta-hCG levels in IVF twin pregnancies should be considered in DS screening to avoid high false positive rates.

Neonatal monitoring after maternal fentanyl analgesia in labor.

OBJECTIVE: To characterize different methods of monitoring neonatal effects associated with maternal opioid analgesia. Special focus was on the static-charge-sensitive bed (SCSB), which could potentially serve as a non-invasive neonatal monitor. METHODS: 12 healthy, term newborns from normal pregnancies were included in this prospective, randomized, controlled study. Maternal labor analgesia was either intravenous fentanyl (n = 5) or paracervical bupivacaine blockade (n = 7). Neonatal recording from delivery to the age of 12 hours included continuous SCSB monitoring with ECG and oximeter for sleep states, respiration, oxygenation, heart rate, and body movements. In addition, umbilical blood pH, Apgar, Amiel-Tison's Neurologic and Adaptive Capacity Scoring (NACS), skin cyanosis scoring, blood pressure, rectal and skin temperatures, and skin blood flow measurements were performed. RESULTS: The study was interrupted, because one baby in the fentanyl group had a significant decrease in oxyhemoglobin saturation (SpO2) to 59%. This was considcred to be residual effect of fentanyl and was treated with naloxone. SpO2 was generally lower in the fentanyl group. Epochs with SpO2 < 90% were more frequent in the fentanyl group, especially during active sleep (mean +/- SD 11.9 +/- 10.7% vs. 2.0 +/- 1.7% of epochs, p = 0.034). Mean heart rate values were lower in the fentanyl group (121.1 +/- 6.4 vs. 132.6 +/- 6.8 beats per minute, p = 0.02), and this difference was seen during wake and all sleep states. Maximum heart rate values were lower in the fentanyl group, too. The opiate group had less quiet sleep than controls (9.6 +/- 2.8% vs. 18.3 +/- 8.3%, p = 0.05). NACS after birth was lower in the fentanyl group (median [range] 15 [13-26] vs. 22 [20-25], p = 0.004). CONCLUSIONS: Several differences were seen between the fentanyl and the control group babies. The SCSB method proved sensitive enough to find neonatal effects of maternal analgesia. Together with ECG and SpO2 monitoring, SCSB gives plentiful information on neonatal well-being in a non-invasive way. Results of this study emphasize the importance of neonatal monitoring after maternal opiate use in labor.

Thromboprophylaxis with low molecular weight heparin (dalteparin) in pregnancy.

Venous thromboembolism remains an important cause of maternal mortality. For women at risk during pregnancy, the recommended venous thromboembolismprophylaxis is unfractionated heparin. Low molecular weight heparins, such as dalteparin, also may be suitable, but randomised trials have not been performed. Pregnant women (105) with confirmed previous or current thromboembolism were randomised to receive either unfractionated heparin twice daily (mean 20569 IU/day) or dalteparin once daily (mean 4631 IU anti-factor Xa units/day) subcutaneously for thromboprophylaxis during pregnancy and postpartum period. Recurrence of venous thromboembolism and safety of treatments were assessed. Dalteparin administered once daily was safe and effective in thromboprophylaxis during pregnancy and postpartum.

Influence of maternal magnesium sulphate and ritodrine treatment on the neonate: a study with six-month follow-up.

Magnesium sulphate and ritodrine are commonly used drugs in the prevention of preterm delivery. However, the effects of these treatments on the newborn are controversial. It has previously been suggested that antenatal tocolytic magnesium sulphate decreases the incidence of cerebral palsy, but increases paediatric mortality. On the other hand, antenatal ritodrine treatment has been reported to increase the incidence of neonatal peri-intra-ventricular haemorrhage (PIVH). We investigated the cerebral ultrasonographic findings, neurological outcome and apparent life-threatening events (ALTE) among 63 infants, born before 33 wk of gestation, whose mothers were antenatally treated for premature birth with ritodrine or magnesium sulphate, and for pre-eclampsia with magnesium sulphate. Cerebral ultrasonography was performed during the first week of life and repeated before hospital discharge. The pathological findings were confirmed by a paediatric radiologist. A paediatrician and a physiotherapist performed the neurological follow-up examination of the survivors at 6 mo of age. We found Grade 3-4 PIVH in 15% of the infants exposed to maternal ritodrine treatment, in 9% of the infants whose mothers received tocolytic magnesium treatment, and in none of those exposed to maternal magnesium treatment for pre-eclampsia (p = 0.19). However, no differences were observed in 6-mo development or in the rate of paediatric mortality and ALTE among these three study groups. Because of the retrospective design and the limited number of subjects, the results of this study must be interpreted with caution.

Prediction of pre-eclampsia with maternal mid-trimester total renin, inhibin A, AFP and free beta-hCG levels.

We wanted to study if maternal serum mid-trimester total renin, inhibin A, AFP or free beta-hCG levels predict the development of pre-eclampsia. Maternal serum alpha-fetoprotein (AFP) and human chorion gonadotrophin (beta-hCG) were evaluated in the screening programme for Down syndrome in 4356 patients prospectively. Data on pregnancy outcome were available in 1242 women. Pregnancy-induced hypertension (PIH) developed in 69 women, 282 women with uneventful pregnancy outcome were selected for controls. Serum total renin and inhibin A levels were measured retrospectively in the trisomy screening samples of 69 and 30 patients who later developed PIH, and in 282 and 7 patients, respectively, who had an uneventful pregnancy outcome. No significant differences were found in the levels of maternal mid-trimester serum total renin, inhibin A or free beta-hCG levels between PIH and healthy women. The multiples of the median (MoM) of AFP values were significantly higher in the subgroup of patients who later developed severe pre-eclampsia than in patients with mild pre-eclampsia or gestational hypertension and healthy pregnant women. Maternal mid-trimester serum levels of total renin, inhibin A and free beta-hCG are not predictive for development of PIH. High mid-trimester serum AFP values may help in the prediction of severe pre-eclampsia.

Expression of nitric oxide synthase in normal and preeclamptic placental tissue and effects of glyceryl trinitrate and shear stress on placental blood flow.

BACKGROUND: To study the expression of constitutively expressed nitric oxide synthase (cNOS) as well as the effects of glyceryl trinitrate (GTN) and shear stress on normal and preeclamptic placental tissue. METHODS: The expression of cNOS was studied using NADPH diaphorase activity reaction in seven normal and four preeclamptic placentas. The effect of GTN (n = 5) and shear stress induced by increasing the flow rate in the perfusion system (n = 5) was studied using an in vitro placental perfusion method. RESULTS: No difference in the distribution of cNOS in placental tissue was found between preeclamptic and normal pregnancies. Shear stress did not affect the production of nitric oxide metabolites. GTN was able to dilate placental vasculature. CONCLUSIONS: cNOS derived from syncytiotrophoblasts may not contribute to the development of preeclampsia. Placental vasculature responds to nitric oxide by vasodilation.