Women and Infants Research Foundation

OBJECTIVE: We aimed to provide information that can be used as a guide to clinicians when advising breastfeeding mothers on normal lactation with regard to the frequency and volume of breastfeedings and the fat content of breast milk. METHODS: Mothers (71) of infants who were 1 to 6 months of age and exclusively breastfeeding on demand test-weighed their infants before and after every breastfeeding from each breast for 24 to 26 hours and collected small milk samples from each breast each time the infant was weighed. RESULTS: Infants breastfed 11 +/- 3 times in 24 hours (range: 6-18), and a breastfeeding was 76.0 +/- 12.6 g (range: 0-240 g), which was 67.3 +/- 7.8% (range: 0-100%) of the volume of milk that was available in the breast at the beginning of the breastfeeding. Left and right breasts rarely produced the same volume of milk. The volume of milk consumed by the infant at each breastfeeding depended on whether the breast that was being suckled was the more or less productive breast, whether the breastfeeding was unpaired, or whether it was the first or second breast of paired breastfeedings; the time of day; and whether the infant breastfed during the night or not. Night breastfeedings were common and made an important contribution to the total milk intake. The fat content of the milk was 41.1 +/- 7.8 g/L (range: 22.3-61.6 g/L) and was independent of breastfeeding frequency. There was no relationship between the number of breastfeedings per day and the 24-hour milk production of the mothers. CONCLUSIONS: Breastfed infants should be encouraged to feed on demand, day and night, rather than conform to an average that may not be appropriate for the mother-infant dyad.

CONTEXT: The polycystic ovary syndrome (PCOS) is the commonest endocrine abnormality in women of reproductive age. OBJECTIVE: To determine the rate of hospital admissions for women with PCOS in Western Australian population in comparison to women without PCOS. DESIGN: A population-based retrospective cohort study using data linkage in a statewide hospital morbidity database system. SETTING: All hospitals within Western Australia. PARTICIPANTS: A total of 2566 women with PCOS hospitalized from 1997-2011 and 25 660 randomly selected age-matched women without a PCOS diagnosis derived from the electoral roll. MAIN OUTCOME MEASURES: Hospitalizations by ICD-10-M diagnoses from 15 years were compared. RESULTS: Hospitalizations were followed until a median age of 35.8 years (interquartile range, 31.0-39.9). PCOS was associated with more nonobstetric and non-injury-related hospital admissions (median, 5 vs 2; P < .001), a diagnosis of adult-onset diabetes (12.5 vs 3.8%), obesity (16.0 vs 3.7%), hypertensive disorder (3.8 vs 0.7%), ischemic heart disease (0.8 vs 0.2%), cerebrovascular disease (0.6 vs 0.2%), arterial and venous disease (0.5 vs 0.2% and 10.4 vs 5.6%, respectively), asthma (10.6 vs 4.5%), stress/anxiety (14.0 vs 5.9%), depression (9.8 vs 4.3%), licit/illicit drug-related admissions (8.8 vs 4.5%), self-harm (7.2 vs 2.9%), land transport accidents (5.2 vs 3.8%), and mortality (0.7 vs 0.4%) (all P < .001). Women with PCOS had a higher rate of admissions for menorrhagia (14.1 vs 3.6%), treatment of infertility (40.9 vs 4.6%), and miscarriage (11.1 vs 6.1%) and were more likely to require in vitro fertilization (17.2 vs 2.0%). CONCLUSION: PCOS has profound medical implications for the health of women, and health care resources should be directed accordingly.

OBJECTIVE: To determine the effect of maternal pre-pregnancy BMI on pregnancy outcomes. METHODS: 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. RESULTS: 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). CONCLUSION: 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: In cross-sectional studies, serum TSH concentrations increase with age. This has not been examined longitudinally, and it is uncertain whether the TSH increase reflects healthy aging or occult thyroid failure. METHODS: We measured serum TSH, free T(4), thyroid peroxidase, and thyroglobulin antibodies in 1100 participants in the 1981 and 1994 Busselton Health Surveys and derived a reference group of 908 individuals without thyroid disease or thyroid antibodies. We examined changes in thyroid function longitudinally and, in 781 participants, explored associations with the CAPZB polymorphism rs10917469. RESULTS: At 13 yr follow-up, mean serum TSH increased from 1.49 to 1.81 mU/liter, a change in mean TSH (ΔTSH) of 0.32 mU/liter [95% confidence interval (CI) 0.27, 0.38, P < 0.001], whereas mean free T(4) concentration was unchanged (16.6 vs. 16.6 pmol/liter, P = 0.7). The TSH increase was most marked in the elderly, such that gender-adjusted ΔTSH increased by 0.08 mU/liter (95% CI 0.04, 0.11) for each decade of baseline age. People with higher baseline TSH values had proportionally smaller increases in TSH, with each additional 1.0 mU/liter of baseline TSH associated with a 0.13 mU/liter decrease (age and gender adjusted) in ΔTSH (95% CI 0.09, 0.16). The ΔTSH did not differ significantly by CAPZB genotype. CONCLUSIONS: Aging is associated with increased serum TSH concentrations, with no change in free T(4) concentrations. The largest TSH increase is in people with the lowest TSH at baseline. This suggests that the TSH increase arises from age-related alteration in the TSH set point or reduced TSH bioactivity rather than occult thyroid disease.

BACKGROUND: Postnatal depression can cause adverse effects on both mother and infant, but its impact on breastfeeding duration is poorly understood. The aim of this study was to investigate the relationship between maternal postnatal depression and breastfeeding duration. METHODS: A cohort of 1745 women was recruited on the postnatal wards of two large Australian obstetric hospitals. Self-report questionnaires were completed at recruitment, and at 2, 6, and 12 months postpartum. Breastfeeding status was determined at each follow-up, and the Edinburgh Postnatal Depression Scale was used to screen for symptoms of depression. Diagnostic psychological interviews were conducted on a subsample of women at each interval. RESULTS: Breastfeeding was initiated by 96 percent of the participants; at 2 months 79 percent were still breastfeeding, 57 percent at 6 months, and 22 percent at 12 months. Of the 18 percent of participants diagnosed with postnatal depression, the onset occurred before 2 months in 63 percent of cases. Median duration of breastfeeding was 26 weeks for women with early-onset depression, 28 weeks for women with late-onset depression, and 39 weeks for women without depression. After adjustment for confounding factors, early cessation of breastfeeding was found to be significantly associated with postnatal depression (adjusted hazard ratio 1.25, 95% CI 1.03-1.52). Onset of postnatal depression occurred before cessation of breastfeeding in most cases. CONCLUSIONS: Postnatal depression has a significant negative impact on breastfeeding duration. Assistance with breastfeeding issues should be included in the management of postnatal depression.

Accurately identifying patients with high-grade serous ovarian carcinoma (HGSOC) who respond to poly(ADP-ribose) polymerase inhibitor (PARPi) therapy is of great clinical importance. Here we show that quantitative BRCA1 methylation analysis provides new insight into PARPi response in preclinical models and ovarian cancer patients. The response of 12 HGSOC patient-derived xenografts (PDX) to the PARPi rucaparib was assessed, with variable dose-dependent responses observed in chemo-naive BRCA1/2-mutated PDX, and no responses in PDX lacking DNA repair pathway defects. Among BRCA1-methylated PDX, silencing of all BRCA1 copies predicts rucaparib response, whilst heterozygous methylation is associated with resistance. Analysis of 21 BRCA1-methylated platinum-sensitive recurrent HGSOC (ARIEL2 Part 1 trial) confirmed that homozygous or hemizygous BRCA1 methylation predicts rucaparib clinical response, and that methylation loss can occur after exposure to chemotherapy. Accordingly, quantitative BRCA1 methylation analysis in a pre-treatment biopsy could allow identification of patients most likely to benefit, and facilitate tailoring of PARPi therapy.

OBJECTIVE: The objective of this study was to determine the influence of birth weight and postnatal weight gain on age at menarche. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort study where girls from the West Australian Pregnancy (Raine) Cohort Study were followed prospectively from fetal life (18 wk of pregnancy) to adolescence (12-14 yr). MAIN OUTCOME MEASURE: Age at menarche was the main outcome measure. RESULTS: Growth status at birth was judged by expected birth weight ratio (EBW; a ratio of observed infant's birth weight over median birth weight appropriate for maternal age, weight, height, parity, infant sex, and gestational age). Postnatal growth status was judged by body mass index (BMI). Both EBW (P = 0.020) and BMI in childhood (8 yr of age) (P < 0.001) were associated with age at menarche. Menarche occurred earlier in girls with lower EBW and higher BMI. CONCLUSIONS: We have demonstrated for the first time that both birth weight and weight gain in childhood are associated with age at menarche. Weight gain before birth and subsequent weight gain up to the age of 8 yr were found to have opposing influences on the timing of menarche. Lower EBW combined with higher BMI during childhood predicted early age at menarche, and this relationship existed across normal birth weight and BMI ranges.

AIM: To investigate pre- and postpartum levels of childbirth fear in a cohort of childbearing women and explore the relationship to birth outcomes. BACKGROUND: While results are mixed, there is evidence that fear of childbirth is associated with mode of birth. Limited theoretical work around childbirth fear has been undertaken with Australian women. DESIGN: A prospective correlation design. Method. Women (n = 401) completed the Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ) version A at 36 weeks gestation, with 243 (61%) women also completing version B at six weeks postpartum. Scores were summarised with means and standard deviations. Content analysis of the free statements identified nine issues of concern. RESULTS: Twenty-six per cent of pregnant women reported low levels of childbirth fear, 48% were moderately fearful and 26% were highly fearful. Fear decreased after birth for those women in the high antenatal fear group, however surgical intervention at birth (n = 238, anova, F(1,230) = 12.39, p = 0.001) and suspected fetal compromise (F(1,230) = 4.33, p = 0.039) increased levels of postpartum fear. Univariately, high antenatal fear was associated with emergency caesarean delivery (n = 324, Wald 5.05, p = 0.025) however after adjustment for nulliparity and fetal compromise the association disappeared. Australian-born women were more likely to report higher levels of fear and experience higher rates of caesarean section than participants of non-Australian origin. CONCLUSIONS: Results support those from earlier studies in showing that nulliparous women experience more fear than parous women before birth and that there is no difference in levels of postpartum fear between these two groups. Fear levels were higher in Australian women when compared to a Swedish sample. RELEVANCE TO CLINICAL PRACTICE: The results of this study add to our preliminary understanding of the phenomena of childbirth fear within an Australian context and are particularly useful in profiling women for whom secondary fear of childbirth is more likely to occur.

OBJECTIVE: To compare the effects of single and repeated courses of corticosteroids on brain growth in fetal sheep. METHODS: Pregnant sheep were given intramuscular betamethasone (0.5 mg/kg) at 104 days' gestation followed at 111, 118, and 124 days by equivalent volumes of sterile normal saline (n = 12) or betamethasone (n = 12). Controls received equivalent volumes of sterile normal saline at all four intervals (n = 12). Lambs were delivered at 125 (preterm) or 145 (term) days. After perfusion, we measured weights (grams) for whole brain, cerebrum, cerebellum, and brain stem, volumes (milliliters) for whole brain and cerebrum, and maximum cerebral anterior-posterior length, width, and depth (centimeters). RESULTS: In the single-injection group at preterm, there were no significant differences (P = .070) in whole-brain weight between the corticosteroid-treated animals (38.0 +/- 1.81 g) and controls (42.5 +/- 1.65 g). Cerebral length and depth were significantly reduced in the corticosteroid group (P < .05); other measures were not significantly different. At term, whole-brain weight was significantly lower (47.5 +/- 1.70 g; P = .022) compared with controls (53.4 +/- 1.73 g). All other measures were significantly reduced (P < .05) except cerebral and brain-stem weights and cerebral length. In the group that received repeated injections at preterm, whole-brain weight was significantly reduced (35.5 +/- 1.65 g; P = .005) compared with controls (42.5 +/- 1.65 g). All other measures were significantly reduced (P < .05) except cerebellar and brain-stem weights. At term, whole-brain weight was also significantly reduced (42.4 +/- 1.52 g; P = .001) compared with controls (53.4 +/- 1.73 g) as were all other measures (P < .05). CONCLUSION: Administration of single and repeated courses of corticosteroids to pregnant sheep retarded fetal brain growth.

Maternal administration of corticosteroids is used to promote lung maturation in human infants considered at risk of preterm delivery [1]. Randomised trials of a single course of corticosteroid treatment have indicated no adverse long-term neurological or cognitive sequelae [2-5]. However, the current trend in many obstetric centres is to use repeated courses in cases where preterm birth has not eventuated, but the risk persists 7 days beyond administration of the original course [6-7]. This practice has not yet been subject to randomised trials of outcome. We have examined the effect of repeated injections of corticosteroids on the development of the optic nerve in prenatal fetal sheep and report a significant delay in the myelination of optic axons. Our results, together with those from other animal studies [8], show that repeated courses of corticosteroids may be detrimental to central nervous system (CNS) development. Clinical practice should balance the known beneficial effects on lung maturation of a single course of corticosteroid against the potential damage to the CNS of repeated courses.

STUDY QUESTION: Is in vitro maturation (IVM) as successful as standard in vitro fertilization (IVF) for the treatment of patients with polycystic ovaries (PCO) in terms of fresh, frozen and cumulative pregnancy outcomes? SUMMARY ANSWER: There was no difference in clinical pregnancy rates in fresh or frozen embryo transfer (FET) cycles between the two treatment groups however, the IVM group showed a lower clinical pregnancy rate cumulatively. There was significantly fewer live births resulting from IVM treatment for both fresh and cumulative cycle outcomes however, there was no difference in live birth rates resulting from FETs between IVM and IVF treatment. WHAT IS KNOWN ALREADY: IVM is well recognized as the only treatment option to eliminate completely the incidence of ovarian hyperstimulation syndrome. However, historically IVM has been less successful than standard IVF in terms of clinical pregnancy, implantation and live birth rates. STUDY DESIGN, SIZE, AND DURATION: This paper represents a retrospective case-control study. The study involved 121 participants who underwent 178 treatment cycles. Cycles were completed between March 2007 and December 2012. All fresh cycles and subsequent FET cycles were included in the analysis to calculate cumulative outcomes. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: All participants were prospectively diagnosed with PCO morphology or polycystic ovarian syndrome (PCOS) and underwent either IVM or standard IVF treatment. Their treatment outcomes were analysed with regard to embryological data, and the rate of biochemical pregnancy, clinical pregnancy and live birth, in addition maternal and neonatal outcomes were assessed. Fifty-six patients underwent 80 cycles of IVM treatment and 65 patients underwent 98 cycles of standard IVF treatment. MAIN RESULTS AND THE ROLE OF CHANCE: For fresh cycles, the differences in the biochemical pregnancy, clinical pregnancy or miscarriage rates between the two treatment groups were not statistically significant. The IVM group showed significantly lower live birth rates in fresh cycles in comparison to standard IVF treatment (18.8 versus 31.0%, P = 0.021). For frozen embryo transfer (FET) cycles the differences in biochemical pregnancy, clinical pregnancy, live birth or miscarriage rates between the two treatments groups were not statistically significant. The cumulative biochemical pregnancy (67.5 versus 83.7%, P = 0.018), clinical pregnancy (51.3 versus 65.3%, P = 0.021) and live birth rates (41.3 versus 55.1%, P = 0.005) were significantly lower in the IVM group in comparison to the standard IVF treatment group. There was no overall difference in the cumulative miscarriage rates between the two treatment groups. There was no difference between treatment methods with regard to the neonatal outcomes, and the IVM group had a significantly lower rate of ovarian hyperstimulation syndrome (0 versus 7.1%, P < 0.001). LIMITATIONS, REASONS FOR CAUTION: This was an observational study and further randomized clinical trials are required to clarify the difference in outcomes between standard IVF and IVM for patients with PCO/PCOS. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to compare IVM with standard IVF in PCO/PCOS patients using blastocyst development and single embryo transfer. Furthermore, it is the first study to show the results of fresh, frozen and cumulative treatment cycle outcomes between the two groups. Our results show similar success rates to those reported from other groups, particularly in relation to the incidence of miscarriage in fresh IVM cycles and improved success from FET cycles. Maternal and neonatal outcomes are consistent with the limited literature available. STUDY FUNDING/COMPETING INTERESTS: The study was supported by the Women's and Infant's Research Foundation of Western Australia. Professor Hart is Medical Director of Fertility Specialists of Western Australia (FSWA) and a shareholder Western IVF. He has received educational sponsorship from MSD, Merck-Serono and Ferring Pharmaceuticals. T.H. is a consultant with FSWA and a shareholder in Western IVF. She has received educational sponsorship from MSD, Merck-Serono and Ferring Pharmaceuticals. The other authors have no competing interests.

OBJECTIVE: Overview of the mechanisms governing gas transport, mechanical factors influencing the transmission of pressure and flow to the lung, and the measurement of lung mechanics during high-frequency oscillatory ventilation (HFOV) in acute respiratory distress syndrome. DATA SOURCES AND STUDY SELECTION: Studies indexed in PubMed illustrating key concepts relevant to the manuscript objectives. Pressure transmission during HFOV in the adult lung was simulated using a published theoretical model. DATA SYNTHESIS: Gas transport during HFOV is complex and involves a range of different mechanisms, including bulk convection, turbulence, asymmetric velocity profiles, pendelluft, cardiogenic mixing, laminar flow with Taylor dispersion, collateral ventilation, and molecular diffusion. Except for molecular diffusion, each mechanism involves generation of convective fluid motion, and is influenced by the mechanical characteristics of the intubated respiratory system and the ventilatory settings. These factors have important consequences for the damping of the oscillatory pressure waveform and the drop in mean pressure from the airway opening to the lung. New techniques enabling partitioning of airway and tissue properties are being developed for measurement of lung mechanics during HFOV. CONCLUSIONS: Awareness of the different mechanisms governing gas transport and the prevailing lung mechanics during HFOV represents essential background for the physician planning to use this mode of ventilation in the adult patient. Monitoring of lung volume, respiratory mechanics, and ventilation homogeneity may facilitate individual optimization of HFOV ventilatory settings in the future.

Antenatal exposure to glucocorticoids, amnionitis, intraamniotic interleukin (IL)-1alpha, or endotoxin can improve postnatal lung function after preterm delivery. The relationship between early lung maturation and the dose and duration of a proinflammatory stimulus has not been evaluated. The effects of proinflammatory stimuli on fetal plasma cortisol also have not been evaluated. We hypothesized that intraamniotic endotoxin would induce early lung maturation in fetal sheep without increasing fetal cortisol. Intraamniotic injections of 1, 4, 20, or 100 mg of Escherichia coli 055:beta5 endotoxin caused 2-fold increases in compliance, 4- to 5-fold increases in lung gas volumes, and 20-fold increases in alveolar saturated phosphatidylcholine (Sat PC) when given 7 d before preterm delivery at 125 d gestation. Animals treated with 20 mg endotoxin for treatment to delivery intervals of 5 h to 15 d had no significant elevations in cord plasma cortisol levels. Increases in Sat PC in lung tissue and alveolar washes were detected 2 d after endotoxin treatment and lung function improved 4 d after endotoxin treatment. Two doses of endotoxin given 3 and 7 d or 7 and 15 d before treatment resulted in lung maturation responses equivalent to single dose comparison groups without elevations in cortisol. Early lung maturation induced by intraamniotic endotoxin in fetal sheep occurred without an increase in fetal plasma cortisol, indicating that endotoxin promoted lung maturation by a mechanism independent of cortisol.

OBJECTIVE: To compare the efficacy and patient satisfaction of three methods of labour induction (double balloon catheters, single balloon catheters and prostaglandin gel) in term nulliparous women with unfavourable cervices. DESIGN: Randomised controlled trial. POPULATION: A total of 330 nulliparous women with unfavourable cervices induced at term. METHODS: Three cervical ripening study arms were used: double balloon catheter (107 women); 16F Foley catheter (110 women) and PGE(2) gel (2 mg) (113 women). MAIN OUTCOME MEASURES: Caesarean section, induction to delivery interval, adverse reactions and patient satisfaction. RESULTS: There was no difference in caesarean delivery rates between groups (double balloon 43%, single balloon 36%, PGE(2) 37%, P = 0.567). The induction to delivery interval was longer in the double balloon group (median 24.5; 95% CI 23.7, 30.6 hours) than the single balloon (23.2; 20.8, 25.8 hours) or PGE(2) (23.8; 21.7, 26.8 hours) (P = 0.043). Uterine hyperstimulation occurred in 14% of the PGE(2) group with none occurring with mechanical cervical ripening. Cord blood gases were worse in the PGE(2) group: median arterial pH double balloon 7.26 (range 7.03-7.40); single balloon 7.26 (7.05-7.44); PGE(2) 7.25 (6.91-7.41) (P = 0.050). Cervical ripening with the single balloon catheter was associated with significantly less pain (pain score > or =4: double balloon 55%, single balloon 36%, PGE(2) 63%, P < 0.001). CONCLUSIONS: Labour induction in nullipara with unfavourable cervices results in high caesarean delivery rates. Although all methods in this study had similar efficacy, the single balloon catheter offers the best combination of safety and patient comfort.

Abstract Objectives: To determine the demographic, environmental, and medical factors that influence the relative weights of the newborn infant and the placenta and compare this ratio with other factors known to predispose to adult ill health. Design: Prospective cohort study. Setting: The tertiary referral centre for perinatal care in Perth, Western Australia. Subjects: 2507 pregnant women who delivered a single live infant at term. Main outcome measures: Placental weight, birth weight, and the ratio of placental weight to birth weight. Results: By multiple regression analysis the placental weight to birthweight ratio was significantly and positively associated with gestational age, female sex, Asian parentage, increasing maternal body mass index, increased maternal weight at booking, lower socioeconomic status, maternal anaemia, and increasing number of cigarettes smoked daily. There were no consistent relations between the placental weight to birthweight ratio and measures of newborn size. Conclusions: The ratio of placental weight to birth weight is not an accurate marker of fetal growth. In its role as a predictor of adult disease the ratio may be acting as a surrogate for other factors which are already known to influence health and may act before or after birth. Determining the role that relative growth rates of the fetus and placenta have in predisposing to adult disease requires prospective study to account for the many confounding variables which complicate this hypothesis. Key messages Retrospective analyses have identified an association between a raised placental weight to birthweight ratio and hypertension in adulthood Accurate estimation of gestational age is crucial when interpreting the placental weight to birthweight ratio Environmental factors associated with alterations in the placental weight to birthweight ratio may not exert their effects exclusively in the antenatal period As a marker of fetal growth the potential usefulness of the placental weight to birthweight ratio is diminished because the ratio is influenced by a multiplicity of factors Prospective study is required to clarify the role of intrauterine programming in the genesis of adult disease

OBJECTIVE: To investigate whether treating periodontal disease prevents preterm birth and other major complications of pregnancy. METHODS: This single-center trial was conducted across six obstetric sites in metropolitan Perth, Western Australia. Pregnant women identified by history to be at risk (n=3,737) were examined for periodontal disease. Approximately 1,000 women with periodontal disease were allocated at random to receive periodontal treatment commencing around 20 weeks of gestation (n=542) or 6 weeks after the pregnancy was completed (controls; n=540). The treatment included mechanical removal of oral biofilms together with oral hygiene instruction and motivation at a minimum of three weekly visits, with further visits if required. RESULTS: There were no differences between the control and treatment groups in preterm birth (9.3% compared with 9.7%, odds ratio [OR] 1.05, 95% confidence interval [CI 0.7-1.58], P=.81), birth weight (3,450 compared with 3,410 g, P=.12), preeclampsia (4.1% compared with 3.4%, OR 0.82, 95% CI 0.44-1.56, P=.55), or other obstetric endpoints. There were four unexplained stillbirths in the control group and no pregnancy losses in the treated group (P=.12). Measures of fetal and neonatal well-being were similar in the two groups, including abnormalities in fetal heart rate recordings (P=.26), umbilical artery flow studies (P=.96), and umbilical artery blood gas values (P=.37). The periodontal treatment was highly successful in improving health of the gums (P<.01). CONCLUSION: The evidence provided by the present study does not support the hypothesis that treatment of periodontal disease during pregnancy in this population prevents preterm birth, fetal growth restriction, or preeclampsia. Periodontal treatment was not hazardous to the women or their pregnancies. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00133926. LEVEL OF EVIDENCE: I.

Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.

UNLABELLED: Idiopathic hydramnios is defined as hydramnios that is not associated with congenital anomalies of the central nervous system or gastrointestinal tract, maternal diabetes, isoimmunizaton, fetal infection (CMV or toxoplasmosis), placental tumors, or multiple gestations. Hydramnios is diagnosed when the AFI is > or = 24 or > or = 25 (> or = 95 or > or = 97.5%), the single deepest pocket (SDP) as being > or = 8, or the examiner's subjective assessment of having an increased amount of amniotic fluid volume. The prevalence of hydramnios is 1%-2% with 50%-60% of those cases as being idiopathic. A PUBMED search from 1950 to 2007 and Science Citation search from 2001 to 2007 revealed only 3 studies that compared pregnancies with idiopathic hydramnios to pregnancies without hydramnios, and 4 studies that evaluated perinatal mortality with hydramnios after correcting for congenital anomalies. Idiopathic hydramnios was found in the larger studies to be linked to fetal macrosomia, an increase in the risk of adverse pregnancy outcomes, and a 2- to 5-fold increase in the risk of perinatal mortality. Tests that may be helpful in the antenatal evaluation of these at-risk pregnancies are: Doppler flow velocimetry of the middle cerebral artery, nonstress test, biophysical profile, and contraction stress test. Prospective studies are needed in this area that is understudied where risk of an adverse pregnancy outcome and perinatal mortality are increased. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to state the prevalence of idiopathic hydramnios, recall the lack of data relating to outcome, explain that there is a 2- to 5-fold increase in the risk of perinatal mortality, and summarize the lack of consensus in monitoring pregnancies afflicted with idiopathic hydramnios.

AIM: To determine population-based rates and outcomes of pre-gestational diabetes mellitus (pre-GDM) and gestational diabetes mellitus (GDM) in pregnancy. METHODS: This was a cross-sectional study, using linked population databases, of all women, and their infants, discharged from hospital following birth in New South Wales (NSW) between 1 July 1998 and 31 December 2002. Women with, and infants exposed to pre-GDM or GDM were compared with those without diabetes mellitus for pregnancy characteristics and outcomes. RESULTS: Women with a singleton pregnancy (n = 370,703) and their infants were included: 1248 women (0.3%) had pre-GDM and 17,128 (4.5%) had GDM. Of those women with pre-GDM, 57% had Type 1 diabetes, 20% had Type 2 diabetes and for 23% the type of diabetes was unknown. Major maternal morbidity or mortality was more common in women with pre-GDM (7.9%) [odds ratio (OR) 3.2, 95% confidence interval (CI) 2.6, 3.9] and in women with GDM (3.1%) (OR 1.2, 95% CI 1.1, 1.4) when compared with women without diabetes (2.6%). Major infant morbidity or mortality occurred more frequently in infants exposed to pre-GDM compared with no diabetes (13.6% vs. 3.1%) (OR 5.0, 95% CI 4.2, 5.8) and in infants exposed to GDM compared with no diabetes (3.2% vs. 2.3%) (OR 1.4, 95% CI 1.3, 1.5). CONCLUSIONS: Pre-GDM and GDM continue to be associated with an increased risk of adverse maternal and neonatal outcomes; however, women with GDM have adverse outcomes less frequently. Rates of GDM and pre-GDM appear to be increasing over time. Clinicians should consider the potential for adverse outcomes, and arrange referral to appropriate services.

BACKGROUND: Diagnosing polycystic ovary syndrome (PCOS) in adolescence is clinically challenging. The prevalence of clinical, ultrasound and biochemical features of PCOS in a community-based adolescent population using current diagnostic criteria has not previously been described. METHODS: This was a prospective cohort study with 244 unselected post-menarchal girls, mean age 15.2 years, of whom 91% were Caucasian. Subjects were recruited from a large population-based birth cohort (the Raine cohort). Clinical hyperandrogenism (HA) was quantified using Ferriman-Gallwey scores. In the early follicular phase (Day 2-6), we measured circulating androgens and sex hormone-binding globulin by immunoassay, and ovarian morphology was assessed by transabdominal ultrasound examination. BMI and waist-hip ratio were measured. RESULTS: Normal ranges for early follicular phase androgens in adolescence were derived for this population. The top 5 and 10% of circulating free testosterone levels were 45.6 and 34.5 pmol/l, respectively. Fifty-one percent of girls reported menstrual irregularity. Clinical HA was uncommon, being observed in only 3.5% of girls. Mean ovarian volume was greater than that reported by others in adult women and 35% of girls had polycystic ovary morphology on transabdominal ultrasound. Taking the upper 5% of free testosterone as HA, 42 girls (18.5%) would have met the Rotterdam criteria for PCOS, 11 girls (5%) the Androgen Excess Society criteria and 7 girls (3.1%) the National Institutes of Health criteria. CONCLUSIONS: Menstrual irregularity is common in adolescence and does not relate to clinical or biochemical HA. Diagnostic criteria for PCOS which include ovarian volume and morphology may be of limited use in adolescence.