Differences in late fetal death rates in association with determinants of small for gestational age fetuses: population based cohort study

Objective: To examine differences in late fetal death rates in association with determinants of small for gestational age fetuses.

The impact of gestational age and fetal weight on the risk of failure of spinal anesthesia for cesarean delivery.

BACKGROUND: There are limited data about spinal dosing for cesarean delivery in preterm parturients. We investigated the hypothesis that preterm gestation is associated with an increased incidence of inadequate spinal anesthesia for cesarean delivery compared with term gestation. METHODS: We searched our perioperative database for women who underwent cesarean delivery under spinal or combined spinal-epidural anesthesia with hyperbaric bupivacaine ⩾10.5mg. The primary outcome was the incidence of inadequate surgical anesthesia needing conversion to general anesthesia or repetition or supplementation of the block. We divided patients into four categories: <28, 28 to <32, 32 to <37 and ⩾37weeks of gestation. The chi-square test was used to compare failure rates and a multivariable regression analysis was performed to investigate potential confounders of the relationship between gestational age and failure. RESULTS: A total of 5015 patients (3387 term and 1628 preterm) were included. There were 278 failures (5.5%). The incidence of failure was higher in preterm versus term patients (6.4% vs. 5.1%, P=0.02). Failure rates were 10.8%, 7.7%, 5.3% and 5% for <28, 28 to <32, 32 to <37 and ⩾37weeks of gestation, respectively. In the multivariable model, low birth weight (P<0.0001), gestational age (P=0.03), ethnicity (P=0.02) and use of combined spinal-epidural anesthesia (P<0.0001) were significantly associated with failure. CONCLUSIONS: At standard spinal doses of hyperbaric bupivacaine used in our practice (⩾10.5mg), there were higher odds of inadequate surgical anesthesia in preterm parturients. When adjusting for potential confounders, low birth weight was the main factor associated with failure.

The association between spastic Cerebral Palsy, intellectual impairment, and gestational age: results from the Northern Ireland Cerebral Palsy Register

Background
Studies suggest a complex relationship between Cerebral Palsy sub-types, severity of impairment, and risk factors such as gestational age. To investigate these relationships, we conducted analyses on over 1,100 children included in the Northern Ireland Cerebral Palsy Register (NICPR) whose clinical CP subtype was Bilateral Spastic or Spastic Hemiplegia, and for whom information was available on the relevant variables.
Methods
We tested for the association between Bilateral and Hemiplegia subtypes, severe intellectual impairment, and gestational age (term; moderately preterm; very or extremely preterm) while controlling for gender, socio-economic deprivation, year of birth, and birth weight (using a standardized birth-weight score based on deviance from the birth weight average within each gestational age band). Severity of intellectual impairment was dichotomised (severe intellectual delay vs. moderate or no delay).
Results
Logistic regressions indicated a good fit of the model, and the predictors included explained approximately 19% of variability in the outcome. The results indicated a strong association between the Bilateral subtype and severe intellectual impairment: compared to children with the Hemiplegia subtype, those with Bilateral Spastic CP displayed a 10-fold increase in the odds of severe intellectual impairment. The results revealed a significant interaction between CP subtype and gestational age: for the Bilateral CP subtype, being born at term was associated with increased probability of severe intellectual impairment.
Discussion
Results are consistent with other studies (Hemming et al., 2008) in indicating that the likelihood of cognitive impairments increases with increasing gestational age at delivery of Bilateral Spastic CP children. The results are discussed in light of hypotheses that suggest the brain might be able to reorganise and compensate the effects of lesions and injuries when it is still less developed.

Cortisol levels in relation to maternal interaction and child internalizing behavior in preterm and full-term children at 18 months corrected age

Cortisol levels were compared in children born preterm at extremely low gestational age (ELGA; 24-28 weeks), very low gestational age (VGLA; 29-32 weeks), and full-term in response to cognitive assessment at 18 months corrected age (CA). Further, we investigated the relationship between maternal interactive behaviors and child internalizing behaviors (rated by the mother) in relation to child cortisol levels. EGLA children had higher "pretest" cortisol levels and a different pattern of cortisol response to cognitive assessment compared to VGLA and full-terms. Higher cortisol levels in ELGA, but not full-term, children were associated with less optimal mother interactive behavior. Moreover, the pattern of cortisol change was related to internalizing behaviors among ELGA, and to a lesser degree VLGA children. In conclusion, our findings suggest altered programming of the hypothalamic-pituitary-adrenal (HPA) axis in preterm children, as well as their greater sensitivity to environmental context such as maternal interactive behavior.

Prenatal and postnatal inflammation in relation to cortisol levels in preterm infants at 18 months corrected age

Objective

To examine whether early inflammation is related to cortisol levels at 18 months corrected age (CA) in children born very preterm.

Study Design

Infants born ≤ 32 weeks gestational age were recruited in the NICU, and placental histopathology, MRI, and chart review were obtained. At 18 months CA developmental assessment and collection of 3 salivary cortisol samples were carried out. Generalized least squares was used to analyze data from 85 infants providing 222 cortisol samples.

Results

Infants exposed to chorioamnionitis with funisitis had a significantly different pattern of cortisol across the samples compared to infants with chorioamnionitis alone or no prenatal inflammation (F[4,139] = 7.3996, P <.0001). Postnatal infections, necrotizing enterocolitis and chronic lung disease were not significantly associated with the cortisol pattern at 18 months CA.

Conclusion

In children born very preterm, prenatal inflammatory stress may contribute to altered programming of the HPA axis.

Keywords: preterm, chorioamnionitis, funisitis, premature infants, hypothalamic-pituitary-adrenal axis, infection, cortisol, stress

Behavioural outcomes at 3 years of age among late preterm infants admitted to neonatal intensive care: a cohort study

Objective: Examine the behavioural outcomes at age 3 years of late preterm infants (LPIs) who were admitted to neonatal intensive care (NIC) in comparison with LPIs who were not admitted.
Method: This cohort study prospectively recruited 225 children born late preterm (34–36+6 weeks gestation) in 2006 in Northern Ireland, now aged 3 years. Two groups were compared: LPIs who received NIC (study; n=103) and LPIs who did not receive NIC (control; n=122). Parents/guardians completed the Child Behaviour Checklist/1½-5. Descriptive maternal and infant data were also collected.
Results: As expected LPI children admitted to NIC had higher medical risk than the non-admitted comparison group (increased caesarean section, born at earlier gestation, lower birth weight and an episode of resuscitation at birth). LPIs admitted to NIC scored higher on the Child Behaviour Checklist/1½-5 compared with those who were not admitted indicating more behavioural problems; this was statistically significant for the Aggressive Behaviour Subscale (z=−2.36) and the Externalising Problems Scale (z=−2.42). The group difference on the Externalising Problems Scale was no longer significant after controlling for gender, gestational age and deprivation score.
Conclusions: This study provides valuable data on the behaviour at age 3 years of LPIs admitted to NIC compared with LPIs not admitted to NIC. Further research would be beneficial to explore medical and psychosocial explanations for observed differences between groups using large prospective cohort studies.

Morphometric study of placental villi and vessels in women with mild hyperglycemia or gestational or overt diabetes

In this study, morphometric measures of placental terminal villi and villous vessels were compared in overt, as well as gestational diabetes mellitus, and mild hyperglycemia diagnosed by oral 100 g glucose tolerance test (100 g-OGTT) and glucose profile (GP). At delivery (gestational age >= 34 weeks) a total of 207 placentas were assigned to a control group (n = 56) or to one of three groups complicated by mild hyperglycemia (n = 5 1), gestational diabetes (n = 59) and overt diabetes (n = 4 1). Placenta samples were randomly selected for blind morphometric assessment with an image analyser. Morphometric measures obtained included area and number of terminal villi and their respective villous vessels. Statistical analyses were performed using the chi-square test, ANOVA and stepwise regression (p <= 0.05). Glycemic means were 86.2 mg/dL in controls, 98.9 mg/dL in mild hyperglycemia, 114.1 mg/dL in gestational diabetes and 122.1 mg/dL in overt diabetes. Our results show that abnormal maternal glycemic levels may change the placental morphometric characteristics related to materno-fetal exchanges. (C) 2007 Elsevier B.V.. All rights reserved.

Comparative study of ultrasonographic methods for assessment of pregnancy age in bitches

Compared with human beings, the application of ultrasound in estimating fetal age in bitches is limited due to the large variation of breed and size in this species. Several formulas were developed to calculate the gestational age and to provide the date of birth in dogs, but the efficacy of these formulas on the different gestational stages and dog breeds is unknown. The aim of this study was to compare sonographic methods for assessment of gestational age and days before parturition in dogs with different body weights and pregnancy stages. Twenty seven bitches of several sizes were examined and divided into three groups according to the initial body weight (A: <10kg; B: 10.1 - 20kg; C: >20.1kg); then each group was divided into three subgroups according to pregnancy stage (1st: 18 to 30 days; 2nd: 31 to 40 days; 3rd: >40 days) estimated according to the first day of copulation. Ultrasonography was performed weekly from the first stage of pregnancy. In the first and second stage the following formulas were applied: GA = (6XGSD) + 20; DBP = 65 - IG; by Nyland & Matton (2002); GA: gestational age; DBP: days before parturition; DSG: gestational sac diameter; in the third stage: DBP = 61,2 - (24,6 X BD); DBP = 43,5 - (10,9 X CD); by Burk & Ackerman (1996); BD: biparietal diameter; CD: body diameter, and: GA = (15 X BD) + 20; GA = (7 X CD) + 29; GA = (6 X BD) + (3 X CD) + 30; DBP = 65 - GA; by Nyland & Matton (2002). Results were compared statistically. The equations proposed by Nyland & Matton (2002), were more accurate in all pregnancy stages, with a margin of error of only three days, regardless of the size of the animal; therefore these methods are the best option in veterinary practice.

Changing presentation of complete hydatidiform mole at the New England Trophoblastic Disease Center over the past three decades: does early diagnosis alter risk for gestational trophoblastic neoplasia?

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Growth of preterm low birth weight infants until 24 months corrected age: effect of maternal hypertension

Objective: To evaluate the growth pattern of low birth weight preterm infants born to hypertensive mothers, the occurrence of growth disorders, and risk factors for inadequate growth at 24 months of corrected age (CA).Methods: Cohort study of preterm low birth weight infants followed until 24 months CA, in a university hospital between January 2009 and December 2010. Inclusion criteria: gestational age < 37 weeks and birth weight of 1,500-2,499g. Exclusion criteria: multiple pregnancies, major congenital anomalies, and loss to follow up in the 2nd year of life. The following were evaluated: weight, length, and BMI. Outcomes: growth failure and risk of overweight at 0, 12, and 24 months CA. Student's t-test, Repeated measures ANOVA (RM-ANOVA), and multiple logistic regression were used.Results: A total of 80 preterm low birth weight infants born to hypertensive mothers and 101 born to normotensive mothers were studied. There was a higher risk of overweight in children of hypertensive mothers at 24 months; however, maternal hypertension was not a risk factor for inadequate growth. Logistic regression showed that being born small for gestational age and inadequate growth in the first 12 months of life were associated with poorer growth at 24 months.Conclusion: Preterm low birth weight born infants to hypertensive mothers have an increased risk of overweight at 24 months CA. Being born small for gestational age and inadequate growth in the 1st year of life are risk factors for growth disorders at 24 months CA. (C) 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Clinical and laboratory characteristics of pregnant women with preeclampsia versus gestational hypertension

To compare clinical and laboratory characteristics, obstetric and perinatal outcomes of patients with pre-eclampsia versus gestational hypertension. A retrospective study was carried out to analyze medical records of patients diagnosed with pre-eclampsia and gestational hypertension whose pregnancies were resolved within a period of 5 years, for a total of 419 cases. We collected clinical and laboratory data, obstetric and perinatal outcomes. Comparisons between groups were performed using the test suitable for the variable analyzed: unpaired t test, Mann-Whitney U test or χ2 test, with the level of significance set at p<0.05. Were evaluated 199 patients in the gestational hypertension group (GH) and 220 patients in the pre-eclampsia group (PE). Mean body mass index was 34.6 kg/m2 in the GH group and 32.7 kg/m2 in the PE group, with a significant difference between groups. The PE group showed higher systolic and diastolic blood pressure and higher rates of abnormal values in the laboratory tests, although the mean values were within the normal range. Cesarean section was performed in 59.1% of cases of PE and in 47.5% of the GH group; and perinatal outcomes in terms of gestational age and birth weight were significantly lower in the PE group. Women with gestational hypertension exhibit epidemiological characteristics of patients at risk for chronic diseases. Patients with pre-eclampsia present clinical and laboratory parameters of greater severity, higher rates of cesarean delivery and worse maternal and perinatal outcomes.

Female Sexual Function and Gestational Diabetes

Introduction. The number of women with gestational diabetes mellitus (GDM) is growing worldwide in parallel with the obesity epidemic. The diagnosis of GDM leads to substantial modifications in the daily routine of these women, and these adjustments could potentially affect their sexual function. There are no previous studies on the sexual function of patients with GDM. Aim. The aim of this study was to investigate the sexual function of patients with GDM in comparison with healthy pregnant women at the same gestational age. Methods. Brazilian women in the third trimester of pregnancy with and without GDM were invited to participate in this cross-sectional study while waiting for their antenatal care visits at a single public tertiary teaching institution between March and December 2010. The Brazilian version of the Female Sexual Function Index (FSFI) questionnaire was used to assess sexual function. Main Outcome Measures. Desire, arousal, lubrication, orgasm, sexual satisfaction, and pain during and after coitus in the last 4 weeks, measured according to a standardized and validated questionnaire. Results. A total of 87 participants were enrolled (43 healthy women and 44 with GDM). There were no significant differences in the sociodemographic characteristics of both groups. The total FSFI scores of GDM patients was 21.0 +/- 9.59 compared with 22.3 +/- 9.17 for healthy women (P = 0.523). Difficulty in desire was the most common sexual dysfunction symptom in both groups, being reported by 42% and 50% of GDM and healthy women, respectively (P = 0.585). Conclusion. The sexual function of Brazilian patients with GDM does not differ significantly from that of healthy pregnant women at the same gestational age. Ribeiro MC, Nakamura MU, Scanavino Mde T, Torloni MR, and Mattar R. Female sexual function and gestational diabetes. J Sex Med 2012; 9: 786-792.

Outcome at two years of age in a Swiss national cohort of extremely preterm infants born between 2000 and 2008

Background While survival rates of extremely preterm infants have improved over the last decades, the incidence of neurodevelopmental disability (ND) in survivors remains high. Representative current data on the severity of disability and of risk factors associated with poor outcome in this growing population are necessary for clinical guidance and parent counselling. Methods Prospective longitudinal multicentre cohort study of preterm infants born in Switzerland between 240/7 and 276/7 weeks gestational age during 2000–2008. Mortality, adverse outcome (death or severe ND) at two years, and predictors for poor outcome were analysed using multilevel multivariate logistic regression. Neurodevelopment was assessed using Bayley Scales of Infant Development II. Cerebral palsy was graded after the Gross Motor Function Classification System. Results Of 1266 live born infants, 422 (33%) died. Follow-up information was available for 684 (81%) survivors: 440 (64%) showed favourable outcome, 166 (24%) moderate ND, and 78 (11%) severe ND. At birth, lower gestational age, intrauterine growth restriction and absence of antenatal corticosteroids were associated with mortality and adverse outcome (p < 0.001). At 360/7 weeks postmenstrual age, bronchopulmonary dysplasia, major brain injury and retinopathy of prematurity were the main predictors for adverse outcome (p < 0.05). Survival without moderate or severe ND increased from 27% to 39% during the observation period (p = 0.02). Conclusions In this recent Swiss national cohort study of extremely preterm infants, neonatal mortality was determined by gestational age, birth weight, and antenatal corticosteroids while neurodevelopmental outcome was determined by the major neonatal morbidities. We observed an increase of survival without moderate or severe disability.

Placental ABCA1 and ABCG1 expression in gestational disease: pre-eclampsia affects ABCA1 levels in syncytiotrophoblasts

INTRODUCTION Transplacental feto-maternal lipid exchange through the ATP-binding cassette transporters ABCA1 and ABCG1 is important for normal fetal development. However, only scarce and conflicting data exist on the involvement of these transporters in gestational disease. METHODS Placenta samples (n = 72) derived from common gestational diseases, including pre-eclampsia (PE), HELLP, intrauterine growth restriction (IUGR), intrahepatic cholestasis of pregnancy and gestational diabetes, were assessed for their ABCA1 and ABCG1 expression levels and compared to age-matched control placentas with qRT-PCR and immunohistochemistry. ABCA1 expression was additionally investigated with immunoblot in placental membrane vesicles. Furthermore, placental cholesterol and phospholipid contents were assessed. RESULTS ABCA1 mRNA levels differed significantly between preterm and term control placentas (p = 0.0013). They were down-regulated in isolated PE and PE with IUGR (p = 0.0006 and p = 0.0012, respectively), but unchanged in isolated IUGR, isolated HELLP and other gestational diseases compared to gestational age-matched controls. Correspondingly, in PE, ABCA1 protein expression was significantly reduced in the apical membrane of the villous syncytiotrophoblast (p = 0.011) and in villous fetal endothelial cells (p = 0.036). Furthermore, in PE there was a significant increase in the placental content of total and individual classes of phospholipids which were partially correlated with diminished ABCA1 expression. Conversely, ABCG1 mRNA and protein levels were stable in the investigated conditions. CONCLUSIONS In gestational disease, there is a specific down-regulation of placental ABCA1 expression at sites of feto-maternal lipid exchange in PE. At a functional level, the increase in placental lipid concentrations provides indirect evidence of an impaired transport capacity of ABCA1 in this disease.