Maternal and perinatal outcomes following pre-Delta, Delta, and Omicron SARS-CoV-2 variants infection among unvaccinated pregnant women in France and Switzerland: a prospective cohort study using the COVI-PREG registry.

Background: SARS-CoV-2 positive pregnant women are at higher risk of adverse outcomes, but little evidence is available on how variants impact that risk. We aim to evaluate maternal and perinatal outcomes among unvaccinated pregnant women that tested positive for SARS-CoV-2, stratified by pre-Delta, Delta, and Omicron periods. Methods: This prospective study enrolled women from March 2020 to September 2022. Exposure to the different SARS-CoV-2 variants was defined by their periods of predominance. The primary outcome was severe maternal adverse outcome defined as either intensive care unit admission, acute respiratory distress syndrome, advanced oxygen supplementation, or maternal death. The secondary outcomes were preterm birth and other perinatal outcomes. Findings: Overall, 1402, 262, and 391 SARS-CoV-2 positive pregnant women were enrolled during the pre-Delta, Delta, and Omicron periods respectively. Severe maternal adverse outcome was reported in 3.4% (n = 947/1402; 95% confidence intervals (95%CI) 2.5-4.5), 6.5% (n = 7/262; 95%CI 3.8-10.2), and 1.0% (n = 4/391; 95%CI 0.3-2.6) of women during the pre-Delta, Delta, and Omicron periods. The risk of severe maternal adverse outcome was higher during the Delta vs pre-Delta period (adjusted risk ratio (aRR) = 1.8; 95%CI 1.1-3.2) and lower during the Omicron vs pre-Delta period (aRR = 0.3; 95%CI, 0.1-0.8). The risks of hospitalization for COVID-19 were 12.6% (n = 176/1402; 95%CI 10.9-14.4), 17.2% (n = 45/262; 95%CI 12.8-22.3), and 12.5% (n = 49/391; 95%CI 9.4-16.2), during the pre-Delta, Delta, and Omicron period, respectively. Pregnancy complications occurred after SARS-CoV-2 exposure in 30.0% (n = 363/1212; 95%CI 27.4-32.6), 35.2% (n = 83/236; 95%CI 29.1-41.6), and 30.3% (n = 105/347; 95%CI 25.5-35.4) of patients during the pre-Delta, Delta, and Omicron periods, respectively. Stillbirths were reported in 0.5% (n = 6/1159; 95%CI 0.2-1.1), 2.8% (n = 6/210; 95%CI 1.0-6.0), and 0.9% (n = 2/213; 95%CI 0.1-3.4) or patients during the pre-Delta, Delta, and Omicron periods respectively. Interpretation: The Delta period was associated with a higher risk of severe maternal adverse outcome and the Omicron period with a lower risk of severe adverse outcome compared to pre-Delta era. The reported risk of hospitalization was high during the Omicron period and should not be trivialized. Funding: Swiss Federal Office of Public Health, Fondation CHUV.

Improving Neonatal and Maternal Outcome by Inducing Mild Labor before Elective Cesarean Section: The Lacarus Randomized Controlled Trial.

BACKGROUND: Newborns delivered by elective cesarean section (CS) are at higher respiratory risk than those delivered vaginally or by CS proceeded by labor (secondary CS). The oxytocin challenge test (OCT) induces uterine contractions that trigger the release of fetal hormones regulating lung fluid clearance during transition from the uterine to an air-breathing environment. OBJECTIVES: The aim is to summarize current evidence and outline the Lacarus trial protocol. METHODS: Literature review informed the design of a randomized placebo-controlled multicenter trial of OCT preceding elective CS in 1,450 women with a singleton pregnancy due for CS at >35 weeks gestation, without preceding contractions, rupture of the membranes, or antenatal steroids. OCT comprises the infusion of oxytocin 5 IU/500 mL Ringer lactate at a rate of 12 mL/h, doubling every 10 min until inducing 5 uterine contractions per 15-min interval. The primary endpoint is the occurrence of neonatal respiratory morbidity within 24 h after birth. Secondary endpoints include biochemical and physiological parameters of fetal and maternal well-being, such as breastfeeding rate and fetal plasma copeptin concentrations. CONCLUSION: This is the first trial to test the hypothesis that oxytocin-induced contractions before elective CS is a promising application of physiologic principles gleaned from natural birth to improve neonatal and maternal outcomes.

Induction of labor and postpartum blood loss.

BACKGROUND: To analyze blood loss after delivery in women with induction of labor compared to women with spontaneous onset of labor. METHODS: In this secondary analysis of a prospective cohort study investigating postpartum hemorrhage, 965 deliveries were analyzed including 380 women with induction of labor (39%) between 2015 and 2016. Primary outcome parameters were rate of postpartum hemorrhage, estimated blood loss and post-partum decrease in hemoglobin. RESULTS: Rates of postpartum hemorrhage and estimated blood loss were not significantly different in women with induction of labor. Women with induction of labor had a significantly reduced decrease in hemoglobin after delivery. In the multivariate linear regression analysis, induction of labor remained associated with reduced decrease in hemoglobin. Secondary maternal and neonatal outcomes were unaffected. CONCLUSIONS: Induction of labor is not associated with increased blood loss after delivery and should not be regarded as a risk factor for postpartum hemorrhage.

Effect of dual tocolysis with fenoterol and atosiban in human myometrium.

Objectives To measure the tocolytic effect of the combination of the oxytocin receptor antagonist atosiban with the ß-mimetic agent fenoterol on human myometrium of pregnant women. Methods An in vitro study of contractility in human myometrium at the Laboratory of the Department of Obstetrics, University Hospital of Zürich, Switzerland, was performed. Thirty-six human myometrial biopsies were obtained during elective caesarean sections of singleton pregnancies at term. Tissue samples were exposed to atosiban, fenoterol and the combination of atosiban with fenoterol. Contractility was measured as area under the curve during 30 min of spontaneous contractions. The effect of treatment was expressed as the percentage of change from basal activity during 30 min of exposure. Differences were calculated using a paired Wilcoxon signed-rank test. An additive effect of dual tocolysis was assumed when no significant difference was detected between the observed and expected inhibition of dual tocolysis. When inhibition was greater or lower than expected, the dual combination was characterised as "synergistic" or "antagonistic", respectively. Results Atosiban and fenoterol alone suppressed contractions by a median of 43.2% and 29.8%, respectively. The combination of atosiban plus fenoterol was measured at a level of 67.3% inhibition. There was no significant difference in the expected (63.2%) and observed inhibition effect of dual tocolysis (P=0.945). Conclusion This study demonstrated an additive effect of dual tocolysis of atosiban and fenoterol on human myometrium in vitro, but no synergistic or antagonistic effect.

[Preeclampsia: New Classifications]. / Präeklampsie: neue Definitionen.

Preeclampsia: New Classifications Abstract. Preeclampsia is a multisystem disease leading to systemic impairment of the maternal endothelial function. A dysbalance of pro- and antiangiogenic factors appears to be significantly involved. The vascular disease leads to the manifestation of symptoms such as arterial hypertension and involvement of end organs such as kidney, liver and brain. The classical diagnostic criterion for arterial hypertension, 'proteinuria' has been downgraded and is no longer obligatory for diagnosis, if other criteria, as maternal organ dysfunction or intrauterine growth retardation, are present. In addition, white-coat hypertension has been included in the classification of hypertension in pregnancy. To classify preeclampsia as 'mild' is being discouraged in the clinical setting to account for the possibility of rapid worsening with significant danger for mother and foetus.

Optimized Sonographic Weight Estimation of Fetuses over 3500 g Using Biometry-Guided Formula Selection.

Purpose The Hadlock et al. formula tends to underestimate fetal weight, in particular > 3500 g. At the high end of the range, the Merz et al. formula is more accurate, but becomes less so in smaller fetuses. This study was designed to improve fetal weight estimation in fetuses > 3500 g by identifying the fetal biometric parameter providing the most reliable guidance to optimal formula selection. Materials and Methods Regression analysis of 12 032 pregnancies showed that multiplication of abdominal circumference by femur length (AC × FL) gave the best choice of appropriate formula: Hadlock for AC × FL < 24 600, Merz for those ≥ 24 600. We then tested this rule, ('Zurich method'), prospectively in 4073 pregnancies, comparing it with the Hadlock, Merz and the Kehl formulas. Birth weights were merged into 7 categories (< 1500 to ≥ 4000 g, interval of 500 g). The percentage error (PE) and absolute percentage error (APE) were calculated. Results The PE using the Zurich method was lower in both > 3500 g groups than with the Hadlock formula alone (3500 - 3999 g: 0.9 % vs. - 5.3 %, > 4000 g: - 3.2 % vs. - 8.6 %), similar to that with the Merz formula alone, and lower than with the Kehl formulas (3500 - 3999 g: - 9.0 % vs. - 3.2 %, > 4000g: - 5.1 % vs. 0.9 %). The Zurich method and Hadlock formula also shared the lowest PE in the < 1500 g group: 0.2 % vs. 6.8 % (Kehl) vs. 9.6 % (Merz). In terms of APE the Zurich method performed almost as well as the Merz formula in the > 4000 g group, while sharing the lowest value with the Hadlock formula in the < 1500 g group (8.2 % vs. 10.5 % [Kehl], 23.6 % [Merz]). Conclusion The Zurich method uses a pivotal value of the biometry parameter AC × FL to switch between formulas and corrects for the errors of the Hadlock formula in fetuses ≥ 3500 g and those of the Merz formula in fetuses < 3500 g.

Risk factors of uterine rupture with a special interest to uterine fundal pressure.

PURPOSE: Uterine rupture is a rare but serious event with a median incidence of 0.09%. Previous uterine surgery is the most common risk factor. The aim of our study was to analyze retrospectively women with uterine rupture during labor and to evaluate postulated risk factors such as uterine fundal pressure (UFP). METHODS: Twenty thousand one hundred and fifty-two deliveries were analyzed retrospectively. Inclusion criteria were 22 weeks and 0 days-42 weeks and 0 days of gestation, singleton pregnancy and cephalic presentation. Women with primary cesarean section were excluded. A logistic regression analysis adjusting for possible risk factors was conducted and a subgroup analysis of women with unscarred uterus was performed. RESULTS: Twenty-eight cases of uterine rupture were identified (incidence: 0.14%). Uterine rupture was noticed in multipara patients only. In the multivariate analysis among all study patients, only previous cesarean section remained a statistically significant risk factor [adjusted odds ration (adj. OR) 12.52 confidence interval (CI) 95% 5.21-30.09]. In the subgroup analysis among women with unscarred uterus (n=19,415) three risk factors were associated with uterine rupture: UFP (adj. OR 5.22 CI 95% 1.07-25.55), abnormal placentation (adj. OR 20.82 CI 95% 2.48-175.16) and age at delivery >40 years (adj. OR 4.77 CI 95% 1.44-15.85). CONCLUSIONS: The main risk factor for uterine rupture in the whole study population is previous uterine surgery. Risk factors in women with unscarred uterus were UFP, abnormal placentation, and age at delivery >40 years. The only factor which can be modified is UFP. We suggest that UFP should be used with caution at least in presence of other supposed risk factors.

Postpartum Blood Loss in Women Treated for Intrahepatic Cholestasis of Pregnancy.

OBJECTIVE: To evaluate postpartum blood loss in women with treated intrahepatic cholestasis of pregnancy. METHODS: In a retrospective case-control study, 15,083 deliveries including 348 women with intrahepatic cholestasis of pregnancy (2.3%) were analyzed from 2004 to 2014. To adjust for differences in baseline characteristics, a propensity analysis was performed and women in the control group were matched to the women in the intrahepatic cholestasis of pregnancy group in a 5:1 ratio. Blood loss was analyzed by estimated blood loss and Δ hemoglobin (Hb, difference between prepartum and postpartum Hb). A subgroup analysis regarding severity of intrahepatic cholestasis of pregnancy based on maximum bile acid level (mild [less than 40 micromoles/L], moderate [40-99 micromoles/L], and severe intrahepatic cholestasis of pregnancy [100 micromoles/L or greater]) was performed. Differences in estimated blood loss, ΔHb, and meconium staining between subgroups were analyzed. A Spearman rank correlation was performed to evaluate the association of bile acid levels and blood loss within subgroups. RESULTS: Estimated blood loss (median 400 [300-600] mL compared with 400 [300-600] mL, P=.22), ΔHb (14.0 [5.0-22.0] compared with 12.0 [4.0-21.0] g/L, P=.09), meconium staining (14.5% compared with 11.4%, P=.12), and number of stillbirths after 26 weeks of gestation (0.6% compared with 1.8%, P=.10) were not significantly different in the study compared with the control group. In moderate and severe intrahepatic cholestasis of pregnancy, meconium staining was observed significantly more often compared with that in a control group (23.0% and 32.3% compared with 11.4%, P<.01). There was no correlation between estimated blood loss or ΔHb and severity of intrahepatic cholestasis of pregnancy. CONCLUSIONS: In our cohort of women with intrahepatic cholestasis of pregnancy who are treated with ursodeoxycholic acid and have planned delivery (induction of labor or planned cesarean delivery) at 38 weeks of gestation, no differences in postpartum blood loss were seen.

Postponed pregnancies and risks of very advanced maternal age.

QUESTIONS UNDER STUDY: To evaluate pregnancy outcome in pregnant women aged ≥45 years, termed very advanced maternal age (VAMA). METHODS: We retrospectively compared the outcome of pregnancies in VAMA patients with controls aged 30 years at time of delivery. Subgroups of singleton and multiple pregnancies were also analysed. Incidences of maternal and fetal adverse outcomes were measured. Statistical significance was set at p <0.05. Odds ratios (ORs) were adjusted where necessary. RESULTS: One hundred and twenty-seven VAMA pregnancies and 2066 control pregnancies of women aged 30 years were analysed. VAMA pregnancies had a higher rate of maternal complications such as gestational hypertension (3.9% vs 0.6%; OR 6.5), preeclampsia (14.2% vs 3.0%; OR 5.4, adjusted OR 4.4) and gestational diabetes (12.6% vs 3.6%; OR 3.8). Likewise, increased need for blood transfusion (3.2% vs 0.7%; OR 4.8, adjusted OR 4.4) and prolonged hospitalisation >7 days (37.8% vs 15.1%; OR 3.42) was found. Infant complications such as prematurity (44.9% vs 16.2%; OR 4.2) and low birthweight <5th percentile (11.0% vs 5.6%; OR 2.1) were also increased. CONCLUSION: Pregnant women of very advanced maternal age (≥45 years) have significantly increased maternal and fetal risks. Women postponing pregnancy or planning a pregnancy in very advanced age should be informed about these risks, in particular before artificial reproductive technologies are applied or "social freezing".

Using a wrap skirt to improve the pelvic examination experience.

INTRODUCTION: The study aims were to analyze the experience of women and their physicians of nakedness when moving between changing room and examination chair and during pelvic examination itself, and to assess the protective benefit of a wrap skirt in alleviating the associated discomfort and vulnerability. MATERIAL AND METHODS: We offered 1000 women a wrap skirt for pelvic examination and asked them to complete a post-procedure questionnaire. Physicians were invited to complete a similar but separate questionnaire. Data were analyzed using chi-squared contingency tables. RESULTS: A total of 425 women (43%, age 15-78 years) completed the questionnaire; 51% felt uncomfortable and embarrassed during the examination, Muslim women significantly more so (p < 0.001). Most women (n = 255; 58%) rated the wrap skirt a significant improvement; 69% requested it for future examinations, significantly more so if the physician was male rather than female (66% vs. 54%, p = 0.003). Even the one-third of women experiencing no discomfort reported improvement. Most examiners (n = 45; 56%) found the wrap skirt beneficial; 31 (38%) were unconvinced. CONCLUSIONS: Pelvic examination as practiced in many countries, on women naked from the waist down throughout, causes unnecessary embarrassment. A simple protective measure, such as a wrap skirt, significantly alleviates the discomfort and sense of vulnerability associated with nakedness.

Maternal and fetal outcomes after uterine fundal pressure in spontaneous and assisted vaginal deliveries.

AIM: This study aimed to evaluate maternal and fetal outcomes after uterine fundal pressure (UFP) in spontaneous and assisted vaginal deliveries. METHODS: In a retrospective cohort study, 9743 singleton term deliveries with cephalic presentation were analyzed from 2004 to 2013. Spontaneous and assisted vaginal deliveries were analyzed separately with and without the application of UFP. Odds ratios were adjusted in a multivariate logistic regression analysis. RESULTS: Prevalence of UFP was 8.9% in spontaneous and 12.1% in assisted vaginal deliveries. UFP was associated with a higher incidence of shoulder dystocia in both spontaneous (adjusted odds ratio [adj. OR] 2.44, confidence interval [CI] 95% 1.23-4.84) and assisted vaginal deliveries (adj. OR 6.88 CI 95% 3.50-13.53). Fetal acidosis (arterial umbilical pH<7.2) was seen more often after the application of UFP in spontaneous vaginal deliveries (adj. OR 3.18, CI 95% 2.64-3.82) and assisted vaginal deliveries (adj. OR 1.59 CI 95% 1.17-2.16). The incidence of 5'-Apgar<7 (adj. OR 2.19 CI 95% 1.04-4.6) and 10'-Apgar<7 (adj. OR 3.04 CI 95% 1.17-7.88) was also increased after the application of UFP in spontaneous deliveries. A higher incidence of anal sphincter tears (AST) (adj. OR 46.25 CI 95% 11.78-181.6) in the UFP group of spontaneous deliveries was observed. CONCLUSIONS: UFP is associated with increased occurrence of shoulder dystocia and fetal acidosis. In spontaneous deliveries, the risk for lower Apgar scores after 5 and 10 min is increased, as well as the risk for AST.

Position at birth as an important factor for the occurrence of anal sphincter tears: a retrospective cohort study.

OBJECTIVE: This work aimed to analyze the association between maternal position at birth in spontaneous deliveries and the occurrence of anal sphincter tears (AST) given the lack of evidence related to the least traumatic birth position. STUDY DESIGN: A total of 7832 vaginal deliveries were included. Vaginal-operative deliveries and deliveries with fundal pressure were excluded. Birth positions on bed, in water, kneeling, and in a squatting position on a low stool were compared. Birth position on bed was considered as the reference group, and a logistic regression analysis adjusting for important fetomaternal parameters was performed. RESULTS: The overall incidence of AST was 1.1%. AST rate was significantly increased in squatting (2.9%) and kneeling (2.1%) positions compared with birth position on bed (1.0%) or in water (0.9%). Logistic regression analysis revealed a significantly higher risk for ASTs in squatting (OR 2.92, CI 95% 1.04-8.18) and in kneeling positions (OR 2.14, CI 95% 1.05-4.37) compared with the reference group on bed. When adjusting for risk factors, birth in a kneeling position remained significantly associated with ASTs (adj. OR 2.21, CI 95% 1.07-4.54). CONCLUSIONS: Birth in squatting or in kneeling position is associated with an elevated risk for ASTs. Birth in water is not associated with an increased risk for AST. Based on the results, women should be informed about the association of certain birth positions with the occurrence of AST.

Kidney-synthesized erythropoietin is the main source for the hypoxia-induced increase in plasma erythropoietin in adult humans.

PURPOSE: Erythropoietin (EPO) is mainly synthesized within renal peritubular fibroblasts, and also other tissues such as the liver possess the ability. However, to what extent non-kidney produced EPO contributes to the hypoxia-induced increase in circulating EPO in adult humans remains unclear. METHODS: We aimed to quantify this by assessing the distribution of EPO glycoforms which are characterized by posttranslational glycosylation patterns specific to the synthesizing cell. The analysis was performed on samples obtained in seven healthy volunteers before, during and after 1 month of sojourn at 3,454 m altitude. RESULTS: Umbilical cord (UC) plasma served as control. As expected a peak (p < 0.05) in urine (2.3 ± 0.5-fold) and plasma (3.3 ± 0.5-fold) EPO was observed on day 1 of high-altitude exposure, and thereafter the concentration decreased for the urine sample obtained after 26 days at altitude, but remained elevated (p < 0.05) by 1.5 ± 0.2-fold above the initial sea level value for the plasma sample. The EPO glycoform heterogeneity, in the urine samples collected at altitude, did not differ from values at sea level, but were markedly lower (p < 0.05) than the mean percent migrated isoform (PMI) for the umbilical cord samples. CONCLUSION: Our studies demonstrate (1) UC samples express a different glycoform distribution as compared to adult humans and hence illustrates the ability to synthesis EPO in non-kidney cells during fetal development (2) as expected hypoxia augments circulating EPO in adults and the predominant source here for remains being kidney derived.

Minimally invasive, imaging guided virtual autopsy compared to conventional autopsy in foetal, newborn and infant cases: study protocol for the paediatric virtual autopsy trial.

BACKGROUND: In light of declining autopsy rates around the world, post-mortem MR imaging is a promising alternative to conventional autopsy in the investigation of infant death. A major drawback of this non-invasive autopsy approach is the fact that histopathological and microbiological examination of the tissue is not possible. The objective of this prospective study is to compare the performance of minimally invasive, virtual autopsy, including CT-guided biopsy, with conventional autopsy procedures in a paediatric population. METHODS/DESIGN: Foetuses, newborns and infants that are referred for autopsy at three different institutions associated with the University of Zurich will be eligible for recruitment. All bodies will be examined with a commercial CT and a 3 Tesla MRI scanner, masked to the results of conventional autopsy. After cross-sectional imaging, CT-guided tissue sampling will be performed by a multifunctional robotic system (Virtobot) allowing for automated post-mortem biopsies. Virtual autopsy results will be classified with regards to the likely final diagnosis and major pathological findings and compared to the results of conventional autopsy, which remains the diagnostic gold standard. DISCUSSION: There is an urgent need for the development of alternative post-mortem examination methods, not only as a counselling tool for families and as a quality control measure for clinical diagnosis and treatment but also as an instrument to advance medical knowledge and clinical practice. This interdisciplinary study will determine whether virtual autopsy will narrow the gap in information between non-invasive and traditional autopsy procedures. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01888380.

Effect of antenatal betamethasone administration on neonatal cardiac autonomic balance.

Beneficial effects of antenatal glucocorticoid treatment in pregnancies at risk for preterm delivery may entail long-term consequences for the establishment of sympathoadrenergic system balance. We analyzed the cardiac autonomic system activity in neonates with a single course of antenatal betamethasone (2 × 12 mg) treatment by calculating heart rate variability (HRV) time-domain parameters from 24 h ECG recordings and short-term frequency-domain parameters during infant active and resting states. In addition, resting and challenged salivary α-amylase levels were measured in 23 betamethasone-exposed neonates and compared with controls. Indicators for overall HRV (SDNN: p = 0.258; triangular index: p = 0.179) and sympathovagal balance [low- to high-frequency power (LF/HF): p = 0.82 (resting state)] were not significantly different in neonates of the betamethasone treatment group. Parameters mostly influenced by sympathetic activity [SD of the average of valid NN intervals (SDANN): p = 0.184 and SDs of all NN intervals (SDNNi): p = 0.784] and vagal tone [RMSSD: p = 1.0; NN50: p = 0.852; HF: p = 0.785 (resting state)] were unaltered. Resting α-amylase levels were not significantly different in the betamethasone treatment group (p = 0.304); however, α-amylase release after a neonatal challenge was slightly reduced (p = 0.045). Thus, cardiac autonomic balance seems to be preserved in neonates exposed to a single course of antenatal betamethasone treatment.

Antenatal betamethasone administration alters stress physiology in healthy neonates.

OBJECTIVE: To analyze hypothalamic-pituitary-adrenal axis balance in healthy newborns after antenatal betamethasone treatment for lung maturation where delivery could be prolonged until or near term. METHODS: In a prospective observational study, salivary cortisol and cortisone levels were measured at the fourth day of life during resting conditions and in response to a pain-induced stress event in 23 neonates with antenatal exposure to a single course of betamethasone (2x12 mg) and compared with 40 controls. The mean interval between betamethasone treatment and delivery was 60+/-23 days. RESULTS: On day 4 of life, neonates in the control group exhibited a significant increase in cortisol and cortisone from baseline levels after the stress induction (1.175-2.4 ng/mL for cortisol and 11.35-18.15 ng/mL for cortisone [both P<.05]), whereas, in betamethasone-exposed neonates, cortisol and cortisone stress response was not significantly different from baseline levels (1.39-1.6 ng/mL for cortisone [P=.76] and 14.8-17.1 ng/mL for cortisol [P=.69]). No influence of gestational age at betamethasone administration (P=.76) or gestational age at delivery (P=.71) on stress response patterns was observed in a multiple stepwise regression. CONCLUSION: A single course of antenatal betamethasone treatment induces a suppression of stress reactivity in healthy newborns.

Blunted stress response in small for gestational age neonates.

There is evidence that adverse conditions during intrauterine development affect future health of the offspring. Hypothalamus-pituitary-adrenal (HPA) axis dysregulation is assumed to play an important role in the association of small for gestational age (SGA) and the pathogenesis of hypertension and the metabolic syndrome. Stress response patterns in SGA neonates may identify a link with intrauterine-induced permanent maladaptation of the HPA axis. Salivary cortisol and cortisone levels were therefore analyzed during resting conditions and in response to a pain-induced stress event in SGA (<5th percentile) and appropriate for gestational age (AGA) neonates born > or =34 wk of gestation. In AGA neonates, salivary cortisol and cortisone levels significantly increased after the stress event (p < 0.05). In contrast, SGA infants exhibited a blunted steroid release after stress induction (p = 0.76, p = 0.65, respectively). No influence of mode of delivery (p = 0.93), gender (p = 0.21), and gestational age (p = 0.57) on stress response patterns was observed in a multiple stepwise regression. SGA neonates show a blunted physiologic activation of the HPA axis in response to a stress stimulus. Thus, intrauterine-induced alteration of HPA axis regulation seems to persist into the postnatal period and represents a prerequisite for the hypothesis of HPA axis involvement in the fetal origin of adult diseases.

Newborn weight charts underestimate the incidence of low birthweight in preterm infants.

OBJECTIVE: The objective of the study was to compare sonographic fetal weight estimates with newborn weight charts and analyze the predictive accuracy of the ponderal index (PI) in preterm infants. STUDY DESIGN: We generated sonographic reference curves for fetal weight and PI estimates from a database of fetal biometric records from 12,589 term deliveries. We then plotted sonographic and newborn weight and PI of 2406 preterm newborns on these curves and compared them with published newborn weight charts. RESULTS: The third centiles of sonographic and newborn weights diverged markedly between 25 and 36 weeks of gestation and by more than 400 g at 32-33 weeks. In contrast, sonographic and newborn PI values were similar despite uncertainties as to fetal length. CONCLUSION: We suggest using sonographic reference fetal weights to screen preterm newborns for low birthweight. Uncertainties in fetal length threaten the reliability of the PI.

Cardiac autonomic balance in small-for-gestational-age neonates.

The cardiac sympathetic nervous system is one putative key factor involved in the intrauterine programming of adult cardiovascular disease. We therefore analyzed cardiac autonomic system activity in small for gestational age (SGA) neonates. Heart rate variability (HRV) from 24-h ECG recordings were analyzed for time-domain and frequency-domain parameters in 27 SGA neonates [median 261 (240-283) days of gestation] compared with 27 appropriate for gestational age (AGA) neonates [median 270 (239-293) days of gestation]. In addition, salivary alpha-amylase levels were analyzed during resting conditions and in response to a pain-induced stress event in 18 SGA [median 266 (240-292) days of gestation] and 34 AGA [median 271 (240-294) days of gestation] neonates. Overall HRV was not significantly different in SGA neonates compared with AGA neonates (SD of all valid NN intervals: P = 0.14; triangular index: P = 0.29), and the sympathovagal balance [low frequency (LF)/high frequency (HF)] was similar (P = 0.62). Parameters mostly influenced by sympathetic activity did not reveal significant differences: (SD of the average of valid NN intervals: P = 0.27; average of the hourly means of SDs of all NN intervals: P = 0.66, LF: P = 0.83) as well as vagal tone-influenced parameters were unaltered (average of the hourly square root of the mean of the sum of the squares of differences between adjacent NN intervals: P = 0.59; proportion of pairs of adjacent NN intervals differing by >50 ms: P = 0.93; HF: P = 0.82). Median resting levels for alpha-amylase were not significantly different in SGA neonates (P = 0.13), and a neonatal stress stimulus revealed similar stress response patterns (P = 0.29). HRV and salivary alpha-amylase levels as indicators of cardiac autonomic activity were not altered in SGA neonates compared with AGA neonates. Thus, it appears that the intrauterine activation of the sympathetic system in SGA fetuses does not directly persist into postnatal life, and neonatal sympathovagal balance appears to be preserved.