The use of antenatal steroid therapy is common in pregnancy. In early pregnancy, steroids may be used in women for the treatment of recurrent miscarriage or fetal abnormalities such as congenital ...adrenal hyperplasia. In mid-late pregnancy, the antenatal administration of corticosteroids to expectant mothers in anticipation of preterm birth is one of the most important advances in perinatal medicine; antenatal corticosteroids are now standard care for pregnancies at risk of premature delivery in high- and middle-income countries. The widespread uptake of this therapy is due to a compelling body of evidence demonstrating improved neonatal outcomes following antenatal corticosteroid exposure, stemming most notably from corticosteroid-driven maturation of fetal pulmonary function. As we approach the 50th anniversary of landmark work in this area by Liggins and Howie, it is apparent that much remains to be understood with regards to how we might best apply antenatal corticosteroid therapy to improve pregnancy outcomes at both early and mid to late gestation.
Drawing on advances in laboratory science, pre-clinical and clinical studies, we performed a narrative review of the scientific literature to provide a timely update on the benefits, risks and uncertainties regarding antenatal corticosteroid use in pregnancy. Three, well-established therapeutic uses of antenatal steroids, namely recurrent miscarriage, congenital adrenal hyperplasia and preterm birth, were selected to frame the review.
Even the most well-established antenatal steroid therapies lack the comprehensive pharmacokinetic and dose-response data necessary to optimize dosing regimens. New insights into complex, tissue-specific corticosteroid signalling by genomic-dependent and independent mechanisms have not been used to inform corticosteroid treatment strategies. There is growing evidence that some fetal corticosteroid treatments are either ineffective, or may result in adverse outcomes, in addition to lasting epigenetic changes in a variety of homeostatic mechanisms. Nowhere is the need to better understand the intricacies of corticosteroid therapy better conveyed than in the findings of Althabe and colleagues who recently reported an increase in overall neonatal mortality and maternal morbidity in association with antenatal corticosteroid administration in low-resource settings.
New research to clarify the benefits and potential risks of antenatal corticosteroid therapy is urgently needed, especially with regard to corticosteroid use in low-resource environments. We conclude that there is both significant scope and an urgent need for further research-informed refinement to the use of antenatal corticosteroids in pregnancy.
To determine the effect of maternal pre-pregnancy BMI on pregnancy outcomes.
Pregnancy cohort recruited pregnancies between 16 and 18 weeks. BMI evaluated underweight, BMI
<
18.5, normal, BMI ...18.5–25, overweight BMI 25–30, and obese BMI
>
30 women.
Pre-pregnancy BMI classified 331 women as underweight (11.7%), 1982 normal (69.9%), 326 overweight (11.5%), and 188 as obese (6.6%). Obese women were more likely to develop gestational diabetes (
p
<
0.001), hypertension (
p
<
0.001), preeclampsia (
p
<
0.001), need labor induction (
p
<
0.001), cesarean delivery for fetal distress (
p
<
0.001), postpartum hemorrhage (
p
=
0.003), need neonatal resuscitation (
p
=
0.001) and deliver hypoglycemic infants (
p
=
0.007). Being underweight is correlated with fetal growth restriction (
p
=
0.001).
Pre-pregnancy obesity is a risk factor for gestational diabetes, preeclampsia, labor induction, cesarean for fetal distress, postpartum hemorrhage and neonatal hypoglycemic and need for resuscitation. Being underweight is risk factor for fetal growth restriction.
Context: The prenatal antecedents of polycystic ovary syndrome (PCOS) are not known, but prenatal androgen exposure is thought to contribute. This has not previously been investigated in large ...prospective studies of normal human pregnancy.
Objective: The aim of the study was to establish the prospective relationship between early life androgen exposure and PCOS in adolescence.
Design and Setting: A prospective cohort study was conducted in the general community.
Patients or Other Participants: A total of 2900 pregnant women were recruited at 18 wk gestation. Prenatal androgen exposure was measured from maternal blood samples (at 18 and 34–36 wk) and umbilical cord blood. Timed (d 2–5 menstrual cycle) blood samples were collected, clinical hyperandrogenism was assessed, and transabdominal ultrasound examination of ovarian morphology was performed in 244 unselected girls from the Raine cohort aged 14–17 yr.
Main Outcome Measure(s): We examined the relationship between early life androgen exposure and PCOS in adolescence.
Results: We did not observe a statistically significant relationship between early life androgen exposure and PCOS in adolescence.
Conclusions: This is the first prospective study to evaluate the relationship between prenatal androgen exposure and PCOS in adolescence in normal pregnancy. Our findings do not support the hypothesis that maternal androgens, within the normal range for pregnancy, directly program PCOS in the offspring.
This large prospective study of maternal and umbilical cord androgen levels failed to demonstrate a relationship between early life androgen exposure and PCOS in adolescence.
BACKGROUND
Periodontal disease (PD) is a common chronic infectious and inflammatory disease of the gums and its supporting tissues, associated with several adverse health outcomes including ...significant obstetric consequences. PD is treatable with good oral hygiene and dental care, and consequently is a modifiable variable that may lead to improvements in adult health. To date, there are no published studies describing the influence of PD on a woman's time to conceive (TTC).
METHODS
This study formed part of the Smile study, which was a multi-centre randomized controlled trial of treatment for PD in mid-pregnancy. PD was defined as the presence of pockets ≥4-mm deep at ≥12 probing sites in fully erupted teeth. At the time of recruitment, women were asked about their TTC and whether they had required fertility treatment.
RESULTS
Of 3737 pregnant women recruited to the study, information was available from 3416 spontaneous conceptions, including 1014 cases with PD (29.7%). Planned pregnancies accounted for 1956 of the 3416 pregnancies available for study. For 146 women, the TTC was >12 months and PD was more prevalent in this group (34.9% versus 25.7%, P = 0.015). The mean TTC in women with PD was 7.1 months confidence interval (CI): 5.7–8.6 compared with 5.0 months (CI: 4.4–5.5, P = 0.019) in those without PD. PD was present in 23.8% of Caucasian women and 41.4% of non-Caucasian women. Compared with Caucasian women without PD, non-Caucasian women with PD had an increased likelihood of TTC >12 months 13.9% versus 6.2%, odds ratio (OR): 2.88 (CI: 1.62–5.12), P < 0.001, but there was no difference for Caucasians with PD (8.6% versus 6.2%, OR: 1.15, CI: 0.74–1.79, P = 0.534). Other simultaneous predictors of TTC >1 year included age, BMI >25 and smoking.
CONCLUSIONS
In the non-Caucasian population, PD was associated with an increased TTC, but whether this is related to PD, or some other factor also present within this population, should be further investigated.
Abstract Aim The significant deterioration of insulin sensitivity and glucose tolerance during pregnancy can have serious health implications for both the pregnant woman and her baby. Although it is ...well established that regular exercise benefits insulin sensitivity in the nonpregnant population, the effect on glucose tolerance in obese pregnant women is not known. The purpose of this study was to investigate the effect of a supervised 10-week, home-based, exercise programme, beginning at week 18 of gestation, on glucose tolerance and aerobic fitness in previously sedentary obese women. Methods Twelve sedentary obese women were randomized into an exercise (EX; n = 6) or control (CON; n = 6) group at 18 weeks of gestation. Those randomized to EX engaged in 10 weeks of supervised home-based exercise (three sessions a week of stationary cycling), while those in the CON group maintained their usual daily activity. Their glucose and insulin responses to an oral glucose tolerance test (OGTT), as well as their aerobic fitness, were assessed both pre- and postintervention. Results Reduced glucose tolerance in the CON, but not EX, group was indicated by a tendency postintervention towards higher blood glucose levels at 1 h of the OGTT ( P = 0.072). Furthermore, at 2 h of the postintervention OGTT, blood glucose tended to remain elevated from baseline in the CON ( P = 0.077). There was also a trend towards increased fitness in the EX ( P = 0.064), but not the CON group. Conclusion Regular aerobic exercise begun during pregnancy may have favourable effects on glucose tolerance and fitness in obese women, and warrants further investigation in a larger sample population.
Please cite this paper as: Robinson M, Oddy W, McLean N, Jacoby P, Pennell CE, de Klerk N, Zubrick S, Stanley F, Newnham J. Low–moderate prenatal alcohol exposure and risk to child behavioural ...development: a prospective cohort study. BJOG 2010;117:1139–1152.
Objective To examine the association of fetal alcohol exposure during pregnancy with child and adolescent behavioural development.
Design The Western Australian Pregnancy Cohort (Raine) Study recruited 2900 pregnancies (1989–91) and the 14‐year follow up was conducted between 2003 and 2006.
Setting Tertiary obstetric hospital in Perth, Western Australia.
Population The women in the study provided data at 18 and 34 weeks of gestation on weekly alcohol intake: no drinking, occasional drinking (up to one standard drink per week), light drinking (2–6 standard drinks per week), moderate drinking (7–10 standard drinks per week), and heavy drinking (11 or more standard drinks per week).
Methods Longitudinal regression models were used to analyse the effect of prenatal alcohol exposure on Child Behaviour Checklist (CBCL) scores over 14 years, assessed by continuous z‐scores and clinical cutoff points, after adjusting for confounders.
Main outcome measure Their children were followed up at ages 2, 5, 8, 10 and 14 years. The CBCL was used to measure child behaviour.
Results Light drinking and moderate drinking in the first 3 months of pregnancy were associated with child CBCL z‐scores indicative of positive behaviour over 14 years after adjusting for maternal and sociodemographic characteristics. These changes in z‐score indicated a clinically meaningful reduction in total, internalising and externalising behavioural problems across the 14 years of follow up.
Conclusions Our findings do not implicate light–moderate consumption of alcohol in pregnancy as a risk factor in the epidemiology of child behavioural problems.
Objective: The objective was to study the effects of repeated antenatal corticosteroids on birth size, growth, and development in preterm infants.
Study Design: This observational study followed up ...for 3 years a prospective geographic cohort in the state of Western Australia of 477 singleton infants born at <33 weeks' gestation.
Results: Birth weight ratio decreased with increasing number of corticosteroid courses (
P = .001), and multivariate analyses confirmed a reduction in birth weight of as much as 9% (
P = .014) and a reduction in head circumference of as much as 4% (
P = .0024). There were no additional benefits in mortality or respiratory outcomes, and there was a trend toward more severe chronic lung disease. At age 3 years growth and severe disability outcomes did not appear to be related to increasing number of corticosteroid courses.
Conclusions: In this cohort study repeated corticosteroid courses were associated with adverse effects on size at birth without apparent benefits. These changes have the potential to affect later development.(Am J Obstet Gynecol 1999;180:114-21.)
Chorioamnionitis is associated with preterm delivery and involution of the fetal thymus. Women at risk of preterm delivery receive antenatal corticosteroids which accelerate fetal lung maturation and ...improve neonatal outcome. However, the effects of antenatal corticosteroids on the fetal thymus in the settings of chorioamnionitis are largely unknown. We hypothesized that intra-amniotic exposure to lipopolysaccharide (LPS) causes involution of the fetal thymus resulting in persistent effects on thymic structure and cell populations. We also hypothesized that antenatal corticosteroids may modulate the effects of LPS on thymic development.
Time-mated ewes with singleton fetuses received an intra-amniotic injection of LPS 7 or 14 days before preterm delivery at 120 days gestational age (term = 150 days). LPS and corticosteroid treatment groups received intra-amniotic LPS either preceding or following maternal intra-muscular betamethasone. Gestation matched controls received intra-amniotic and maternal intra-muscular saline. The fetal intra-thoracic thymus was evaluated.
Intra-amniotic LPS decreased the cortico-medullary (C/M) ratio of the thymus and increased Toll-like receptor (TLR) 4 mRNA and CD3 expression indicating involution and activation of the fetal thymus. Increased TLR4 and CD3 expression persisted for 14 days but Foxp3 expression decreased suggesting a change in regulatory T-cells. Sonic hedgehog and bone morphogenetic protein 4 mRNA, which are negative regulators of T-cell development, decreased in response to intra-amniotic LPS. Betamethasone treatment before LPS exposure attenuated some of the LPS-induced thymic responses but increased cleaved caspase-3 expression and decreased the C/M ratio. Betamethasone treatment after LPS exposure did not prevent the LPS-induced thymic changes.
Intra-amniotic exposure to LPS activated the fetal thymus which was accompanied by structural changes. Treatment with antenatal corticosteroids before LPS partially attenuated the LPS-induced effects but increased apoptosis in the fetal thymus. Corticosteroid administration after the inflammatory stimulus did not inhibit the LPS effects on the fetal thymus.
The chorioamnionitis associated with preterm delivery is often polymicrobial with ureaplasma being the most common isolate. To evaluate interactions between the different proinflammatory mediators, ...we hypothesized that ureaplasma exposure would increase fetal responsiveness to LPS. Fetal sheep were given intra-amniotic (IA) injections of media (control) or Ureaplasma parvum serovar 3 either 7 or 70 d before preterm delivery. Another group received an IA injection of Escherichia coli LPS 2 d prior to delivery. To test for interactions, IA U. parvum-exposed animals were challenged with IA LPS and delivered 2 d later. All animals were delivered at 124 ± 1-d gestation (term = 150 d). Compared with the 2-d LPS exposure group, the U. parvum 70 d + LPS group had 1) decreased lung pro- and anti-inflammatory cytokine expression and 2) fewer CD3(+) T lymphocytes, CCL2(+), myeloperoxidase(+), and PU.1(+) cells in the lung. Interestingly, exposure to U. parvum for 7 d did not change responses to a subsequent IA LPS challenge, and exposure to IA U. parvum alone induced mild lung inflammation. Exposure to U. parvum increased pulmonary TGF-β1 expression but did not change mRNA expression of either the receptor TLR4 or some of the downstream mediators in the lung. Monocytes from fetal blood and lung isolated from U. parvum 70 d + LPS but not U. parvum 7 d + LPS animals had decreased in vitro responsiveness to LPS. These results are consistent with the novel finding of downregulation of LPS responses by chronic but not acute fetal exposures to U. parvum. The findings increase our understanding of how chorioamnionitis-exposed preterm infants may respond to lung injury and postnatal nosocomial infections.
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