Intravenous iron versus blood transfusion for postpartum anemia: a systematic review and meta-analysis.

BACKGROUND: Intravenous iron (IV-iron) is used as an alternative to, or alongside, red blood cell transfusion (RBC-T) to treat more severe postpartum anemia (PPA), although optimal treatment options remain unclear. No previous systematic reviews have examined IV-iron and RBC-T, including patient-reported outcomes and hematological responses. METHODS: A systematic review and meta-analysis of randomized trials comparing IV-iron and RBC-T with each other, oral iron, no treatment, and placebo for the treatment of PPA. Key inclusion criteria were PPA (hemoglobin < 12 g/dL) and IV-iron or RBC-T as interventions. Key exclusion criteria were antenatal IV-iron or RBC-T. Fatigue was the primary outcome. Secondary outcomes included hemoglobin and ferritin concentrations, and adverse events. From 27th August 2020 to 26th September 2022, databases, registries, and hand searches identified studies. A fixed-effect meta-analysis was undertaken using RevMan (5.4) software. The quality of the studies and the evidence was assessed using the Cochrane Risk of Bias table, and Grading of Recommendations, Assessment, Development, and Evaluation. This review is registered with the Prospective Register of Systematic Reviews (CRD42020201115). RESULTS: Twenty studies and 4196 participants were included: 1834 assigned IV-iron, 1771 assigned oral iron, 330 assigned RBC-T, and 261 assigned non-intervention. Six studies reported the primary outcome of fatigue (1251 participants). Only studies of IV-iron vs. oral iron (15 studies) were available for meta-analysis. Of these, three reported on fatigue using different scales; two were available for meta-analysis. There was a significant reduction in fatigue with IV-iron compared to oral iron (standardized mean difference - 0.40, 95% confidence interval (CI) - 0.62, - 0.18, I2 = 0%). The direction of effect also favored IV-iron for hemoglobin (mean difference (MD) 0.54 g/dL, 95% confidence interval (CI) 0.47, 0.61, I2 = 91%), ferritin, (MD 58.07 mcg/L, 95% CI 55.74, 60.41, I2 = 99%), and total adverse events (risk-ratio 0.63, 95% CI 0.52, 0.77, I2 = 84%). The overall quality of the evidence was low-moderate. DISCUSSION: For all outcomes, the evidence for RBC-T, compared to IV-iron, non-intervention, or dose effects of RBC-T is very limited. Further research is needed to determine whether RBC-T or IV-iron for the treatment of PPA is superior for fatigue and hematological outcomes.

What is Known About Critical Congenital Heart Disease Diagnosis and Management Experiences from the Perspectives of Family and Healthcare Providers? A Systematic Integrative Literature Review.

The experience of diagnosis, decision-making and management in critical congenital heart disease is layered with complexity for both families and clinicians. We synthesise the current evidence regarding the family and healthcare provider experience of critical congenital heart disease diagnosis and management. A systematic integrative literature review was conducted by keyword search of online databases, MEDLINE (Ovid), PsycINFO, Cochrane, cumulative index to nursing and allied health literature (CINAHL Plus) and two journals, the Journal of Indigenous Research and Midwifery Journal from 1990. Inclusion and exclusion criteria were applied to search results with citation mining of final included papers to ensure completeness. Two researchers assessed study quality combining three tools. A third researcher reviewed papers where no consensus was reached. Data was coded and analysed in four phases resulting in final refined themes to summarise the findings. Of 1817 unique papers, 22 met the inclusion criteria. The overall quality of the included studies was generally good, apart from three of fair quality. There is little information on the experience of the healthcare provider. Thematic analysis identified three themes relating to the family experience: (1) The diagnosis and treatment of a critical congenital heart disease child significantly impacts parental health and wellbeing. (2) The way that healthcare and information is provided influences parental response and adaptation, and (3) parental responses and adaptation can be influenced by how and when support occurs. The experience of diagnosis and management of a critical congenital heart disease child is stressful and life-changing for families. Further research is needed into the experience of minority and socially deprived families, and of the healthcare provider, to inform potential interventions at the healthcare provider and institutional levels to improve family experience and support.

New Zealand women's experiences of managing gestational diabetes through diet: a qualitative study.

BACKGROUND: For women with gestational diabetes mellitus (GDM) poor dietary choices can have deleterious consequences for both themselves and their baby. Diet is a well-recognised primary strategy for the management of GDM. Women who develop GDM may receive dietary recommendations from a range of sources that may be inconsistent and are often faced with needing to make several dietary adaptations in a short period of time to achieve glycaemic control. The aim of this study was to explore how women diagnosed with GDM perceive dietary recommendations and how this information influences their dietary decisions during pregnancy and beyond. METHODS: Women diagnosed with GDM before 30 weeks' gestation were purposively recruited from two GDM clinics in Auckland, New Zealand. Data were generated using semi-structured interviews and thematic analysed to identify themes describing women's perceptions and experiences of dietary recommendations for the management of GDM. RESULTS: Eighteen women from a diverse range of sociodemographic backgrounds participated in the study. Three interconnected themes described women's perceptions of dietary recommendations and experiences in managing their GDM through diet: managing GDM is a balancing act; using the numbers as evidence, and the GDM timeframe. The primary objective of dietary advice was perceived to be to control blood glucose levels and this was central to each theme. Women faced a number of challenges in adhering to dietary recommendations. Their relationships with healthcare professionals played a significant role in their perception of advice and motivation to adhere to recommendations. Many women perceived the need to follow dietary recommendations to be temporary, with few planning to continue dietary adaptations long-term. CONCLUSIONS: The value of empathetic, individually tailored advice was highlighted in this study. A greater emphasis on establishing healthy dietary habits not just during pregnancy but for the long-term health of both mother and baby is needed.

Body composition of New Zealand-born term babies differs by ethnicity, gestational age and sex.

BACKGROUND: Body composition provides important information on nutrition and future metabolic risk. New Zealand has a diverse ethnic population for which there are no newborn body composition data. AIM: To determine body composition in a cohort of New Zealand-born term babies. STUDY DESIGN: Observational study. SUBJECTS: Healthy, term infants between 37+0 and 41+6 weeks' gestation in two hospitals in Auckland, New Zealand. OUTCOME MEASURES: Body composition by air displacement plethysmography and anthropometry measured within 5 days of birth. Parent-identified ethnicity was prioritised according to Ministry of Health criteria. Data were analysed using t-test, ANOVA with Tukey post-hoc tests, quantile regression and are mean(SD). RESULTS: 440 babies (54% male) were included. Pacific Island/Maori (PI/M) were heavier at birth than Asian/Middle Eastern/Latin American/African (Asian+) babies (3403(506) vs 3181(485) g, p < .05). PI/M and European (E) babies were longer with larger head and waist circumferences than Asian+ babies (all p < .05). Absolute fat mass (FM) was not different amongst ethnicities (E, 365(156), PI/M, 347(183), Asian+, 357(188) g) but PI/M babies had significantly lower FM% than Asian+ (9.8(4.3) vs 10.9(4.5) %, p < .05). Fat-free mass (FFM) was greater in PI/M (3056(400) g) than E (2952(345) g (p < .05) and both PI/M and E had greater FFM than Asian+ (2824(363) g, p < .05). Early term babies had less FFM than term and late-term babies (2732(370), 3012(352), 3173(302)g, p < .001) respectively. CONCLUSIONS: Asian+ babies were the smallest babies with the least FFM yet had similar FM and the highest FM%, indicative of a thin, fat phenotype from birth.

Variation in outcome reporting in randomized controlled trials of interventions for prevention and treatment of fetal growth restriction.

OBJECTIVE: Although fetal growth restriction (FGR) is well known to be associated with adverse outcomes for the mother and offspring, effective interventions for the management of FGR are yet to be established. Trials reporting interventions for the prevention and treatment of FGR may be limited by heterogeneity in the underlying pathophysiology. The aim of this study was to conduct a systematic review of outcomes reported in randomized controlled trials (RCTs) assessing interventions for the prevention or treatment of FGR, in order to identify and categorize the variation in outcome reporting. METHODS: MEDLINE, EMBASE and The Cochrane Library were searched from inception until August 2018 for RCTs investigating therapies for the prevention and treatment of FGR. Studies were assessed systematically and data on outcomes that were reported in the included studies were extracted and categorized. The methodological quality of the included studies was assessed using the Jadad score. RESULTS: The search identified 2609 citations, of which 153 were selected for full-text review and 72 studies (68 trials) were included in the final analysis. There were 44 trials relating to the prevention of FGR and 24 trials investigating interventions for the treatment of FGR. The mean Jadad score of all studies was 3.07, and only nine of them received a score of 5. We identified 238 outcomes across the included studies. The most commonly reported were birth weight (88.2%), gestational age at birth (72.1%) and small-for-gestational age (67.6%). Few studies reported on any measure of neonatal morbidity (27.9%), while adverse effects of the interventions were reported in only 17.6% of trials. CONCLUSIONS: There is significant variation in outcome reporting across RCTs of therapies for the prevention and treatment of FGR. The clinical applicability of future research would be enhanced by the development of a core outcome set for use in future trials. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Postnatal effects of intrauterine treatment of the growth-restricted ovine fetus with intra-amniotic insulin-like growth factor-1.

KEY POINTS: Fetal growth restriction increases the risk of fetal and neonatal mortality and morbidity, and contributes to increased risk of chronic disease later in life. Intra-amniotic insulin-like growth factor-1 (IGF1) treatment of the growth-restricted ovine fetus improves fetal growth, but postnatal effects are unknown. Here we report that intra-amniotic IGF1 treatment of the growth-restricted ovine fetus alters size at birth and mechanisms of early postnatal growth in a sex-specific manner. We also show that maternal plasma C-type natriuretic peptide (CNP) products are related to fetal oxygenation and size at birth, and hence may be useful for non-invasive monitoring of fetal growth restriction. Intrauterine IGF1 treatment in late gestation is a potentially clinically relevant intervention that may ameliorate the postnatal complications of fetal growth restriction. ABSTRACT: Placental insufficiency-mediated fetal growth restriction (FGR) is associated with altered postnatal growth and metabolism, which are, in turn, associated with increased risk of adult disease. Intra-amniotic insulin-like growth factor-1 (IGF1) treatment of ovine FGR increases growth rate in late gestation, but the effects on postnatal growth and metabolism are unknown. We investigated the effects of intra-amniotic IGF1 administration to ovine fetuses with uteroplacental embolisation-induced FGR on phenotypical and physiological characteristics in the 2  weeks after birth. We measured early postnatal growth velocity, amino-terminal propeptide of C-type natriuretic peptide (NTproCNP), body composition, tissue-specific mRNA expression, and milk intake in singleton lambs treated weekly with 360 µg intra-amniotic IGF1 (FGRI; n = 13 females, 19 males) or saline (FGRS; n = 18 females, 12 males) during gestation, and in controls (CON; n = 15 females, 22 males). There was a strong positive correlation between maternal NTproCNP and fetal oxygenation, and size at birth in FGR lambs. FGR lambs were ∼20% lighter at birth and demonstrated accelerated postnatal growth velocity. IGF1 treatment did not alter perinatal mortality, partially abrogated the reduction in newborn size in females, but not males, and reduced accelerated growth in both sexes. IGF1-mediated upregulation of somatotrophic genes in males during the early postnatal period could suggest that treatment effects are associated with delayed axis maturation, whilst treatment outcomes in females may rely on the reprogramming of nutrient-dependent mechanisms of growth. These data suggest that the growth-restricted fetus is responsive to intra-amniotic intervention with IGF1, and that sex-specific somatotrophic effects persist in the early postnatal period.

Probabilistic description of infant head kinematics in abusive head trauma.

Abusive head trauma (AHT) is a potentially fatal result of child abuse, but the mechanisms by which injury occur are often unclear. To investigate the contention that shaking alone can elicit the injuries observed, effective computational models are necessary. The aim of this study was to develop a probabilistic model describing infant head kinematics in AHT. A deterministic model incorporating an infant's mechanical properties, subjected to different shaking motions, was developed in OpenSim. A Monte Carlo analysis was used to simulate the range of infant kinematics produced as a result of varying both the mechanical properties and the type of shaking motions. By excluding physically unrealistic shaking motions, worst-case shaking scenarios were simulated and compared to existing injury criteria for a newborn, a 4.5 month-old, and a 12 month-old infant. In none of the three cases were head kinematics observed to exceed previously-estimated subdural haemorrhage injury thresholds. The results of this study provide no biomechanical evidence to demonstrate how shaking by a human alone can cause the injuries observed in AHT, suggesting either that additional factors, such as impact, are required, or that the current estimates of injury thresholds are incorrect.

Intrauterine Intervention for the Treatment of Fetal Growth Restriction.

Fetal growth restriction (FGR) is associated with an increased incidence of fetal and neonatal death, and of neonatal morbidity. Babies born following FGR also are at risk of a range of postnatal complications, which may contribute to an increased incidence of disease later in life. There currently are no effective clinical interventions which improve perinatal survival, intrauterine growth and later outcomes of the FGR baby. Postnatal interventions aimed at promoting or accelerating growth in FGR babies to improve outcome, particularly neurodevelopmental outcomes, may further increase the risk of metabolic dysregulation and, therefore, the risk of developing chronic disease in adulthood. An intrauterine intervention to improve nutrition and growth in the FGR fetus may have the potential to decrease mortality and improve long-term outcomes by delaying preterm delivery and mitigating the need for and risks of accelerated postnatal growth.

Head kinematics during shaking associated with abusive head trauma.

Abusive head trauma (AHT) is a potentially fatal result of child abuse but the mechanisms of injury are controversial. To address the hypothesis that shaking alone is sufficient to elicit the injuries observed, effective computational and experimental models are necessary. This paper investigates the use of a coupled rigid-body computational modelling framework to reproduce in vivo shaking kinematics in AHT. A sagittal plane OpenSim computational model of a lamb was developed and used to interpret biomechanical data from in vivo shaking experiments. The acceleration of the head during shaking was used to provide in vivo validation of the associated computational model. Results of this study demonstrated that peak accelerations occurred when the head impacted the torso and produced acceleration magnitudes exceeding 200ms(-)(2). The computational model demonstrated good agreement with the experimental measurements and was shown to be able to reproduce the high accelerations that occur during impact. The biomechanical results obtained with the computational model demonstrate the utility of using a coupled rigid-body modelling framework to describe infant head kinematics in AHT.

Do recommended protein intakes improve neurodevelopment in extremely preterm babies?

OBJECTIVE: To determine whether achieving recommended protein intakes for extremely low birthweight (ELBW; birth weight <1000 g) babies, resulting in better growth, improves neurodevelopmental outcomes. DESIGN: A prospective cohort study of ELBW babies before and after the introduction of a new nutritional policy designed to meet international consensus protein recommendations. Forty-five children born 'before' and 42 born 'after' the policy change were assessed at 2 years' corrected age (CA). Associations between nutritional intakes, growth and neurodevelopmental outcome (Bayley Scales of Infant and Toddler Development, Third edition (Bayley-III), motor and sensory impairment) were assessed using univariate and multivariate analyses. RESULTS: Bayley-III cognitive (mean (SD) 96 (12) vs 96 (15)), motor (96 (13) vs 95 (15)) or language scores (89 (11) vs 91 (17)) were not different between the 'before' and 'after' cohorts. In the 'before' cohort, motor scores were positively associated with enteral nutrition intakes and growth velocity. Neither were sensory impairments different between groups (visual impairment 4 vs 2, hearing impairment 2 vs 0) nor was the gross motor function classification score (any cerebral palsy 2 vs 1). CONCLUSIONS: In this prospective cohort study, increasing intravenous and enteral protein intakes to recommended levels in the first month after birth was not associated with improved cognitive, language or motor scores or decreased sensory impairments at 2 years' CA despite significantly improved early growth and reduced postnatal faltering growth. Appropriate randomised controlled trials are needed to answer definitively whether higher early protein intakes improve neurodevelopmental outcome in this population.

Maternal insulin sensitivity in midpregnancy does not determine birth weight after embryo transfer between large and small breed sheep.

Embryo transfer of large sheep breed embryos (Suffolk) into small breed ewes (Cheviot) constrains birth size, but the maternal factors influencing fetal growth restriction are unknown. We hypothesized that reciprocal embryo transfer crosses between breeds of divergent size would affect pregnancy-related development of maternal insulin resistance in midgestation, thereby influencing fetal growth. Following superovulation, embryos were surgically collected 6 d postmating and transferred to recipients on the same day. Between- and within-breed transfers were performed. Between 60 and 70 d of pregnancy overnight-fasted ewes underwent hyperinsulinemic-euglycemic clamps for assessment of insulin sensitivity. Maternal insulin sensitivity did not vary with transferred lamb breed. Overall, Cheviot ewes tended to have higher fasting glucose (P = 0.068), fasting insulin (P = 0.052), and steady-state glucose (P = 0.065) concentrations than Suffolk ewes at the stage of pregnancy studied. As expected, transferred between-breed Suffolk lambs were born lighter (P = 0.014), and transferred between-breed Cheviot lambs tended to be heavier at birth (P = 0.056) than respective lambs transferred within breed. Midgestation insulin sensitivity does not appear to be a major factor constraining growth of large breed sheep fetus transferred into smaller breed or a factor in releasing constraint in growth of a small breed fetus within a larger breed ewe. However, as embryo size is already different between transferred groups by 19 d, factors other than maternal gestational insulin resistance may determine fetal growth in this embryo transfer paradigm.

The importance of early life in childhood obesity and related diseases: a report from the 2014 Gravida Strategic Summit.

Obesity and its related non-communicable diseases (NCDs), such as type 2 diabetes, heart disease and cancer, impose huge burdens on society, particularly the healthcare system. Until recently, public health and policy were primarily focused on secondary prevention and treatment of NCDs. However, epidemiological and experimental evidence indicates that early-life exposures influence the risk of childhood obesity and related diseases later in life, and has now focused attention on the health of both mother and child. During pregnancy and the early neonatal period, individuals respond to their environment by establishing anatomical, physiological and biochemical trajectories that shape their future health. This period of developmental plasticity provides an early window of opportunity to mitigate the environmental insults that may increase an individual's sensitivity to, or risk of, developing obesity or related diseases later in life. Although much investigation has already occurred in the area of Developmental Origins of Health and Disease research, the science itself is still in its infancy. It remains for researchers to tackle the important outstanding questions and translate their knowledge into workable solutions for the public good. The challenge, however, is to decide which areas to focus on. With these opportunities and challenges in mind, the 2014 Gravida Summit convened to examine how its early-life research program can determine which areas of research into mechanisms, biomarkers and interventions could contribute to the international research strategy to fight childhood obesity and its related diseases.

Fetal growth factors and fetal nutrition.

Optimal fetal growth is important for a healthy pregnancy outcome and also for lifelong health. Fetal growth is largely regulated by fetal nutrition, and mediated via the maternal and fetal glucose/insulin/insulin-like growth factor axes. Fetal nutrition may reflect maternal nutrition, but abnormalities of placental function can also affect fetal growth, as the placenta plays a key intermediary role in nutritional signalling between mother and fetus. Fetal nutrition also impacts on the development of key fetal endocrine systems such as the glucose-insulin and insulin-like growth factor axes. This is likely to contribute to the link between both fetal growth restriction and fetal overgrowth, and increased risks of obesity and impaired glucose tolerance in later life. This review focuses on the associations between maternal and fetal nutrition, fetal growth and later disease risk, with particular emphasis on the role of insulin-like growth factors and the importance of the periconceptional period.

Periconceptional undernutrition in sheep leads to decreased locomotor activity in a natural environment.

Maternal undernutrition during pregnancy increases offspring obesity and metabolic disease risk. We hypothesized that periconceptional undernutrition in sheep from 60 days before conception through to day 30 of gestation (UN) would decrease voluntary locomotor activity in adult offspring. Distance travelled was measured at 18 months of age for ∼48 h in the paddock. Data were analysed using multiple regression analysis, with explanatory variables including sex, nutrition group, birth weight, average time between GPS measurements and percentage of time during the measurement period spent in daylight. Mean (±s.e.) distance walked (m/h) was greater for control (CON) than UN animals, and greater for females than males [110.2 (6.5), CON females; 110.7 (6.3), CON males; 105.1 (5.3), UN females and 95.5 (5.8), UN males; P = 0.02 for nutrition group effect and for sex effect]. Periconceptional undernutrition may lead to a significant decrease in voluntary physical activity in adult offspring.

Optimum feeding and growth in preterm neonates.

Approximately 10% of all babies worldwide are born preterm, and preterm birth is the leading cause of perinatal mortality in developed countries. Although preterm birth is associated with adverse short- and long-term health outcomes, it is not yet clear whether this relationship is causal. Rather, there is evidence that reduced foetal growth, preterm birth and the long-term health effects of both of these may all arise from a suboptimal intrauterine environment. Further, most infants born preterm also experience suboptimal postnatal growth, with potential adverse effects on long-term health and development. A number of interventions are used widely in the neonatal period to optimise postnatal growth and development. These commonly include supplementation with macronutrients and/or micronutrients, all of which have potential short-term risks and benefits for the preterm infant, whereas the long-term health consequences are largely unknown. Importantly, more rapid postnatal growth trajectory (and the interventions required to achieve this) may result in improved neurological outcomes at the expense of increased cardiovascular risk in later life.

Size at birth and adult fat mass in twin sheep are determined in early gestation.

Size at birth is related to adult health outcomes. Twins are born smaller than singletons; this has been assumed to be secondary to limited nutrient supply in late gestation.We hypothesised that growth trajectory in twins, and the adult consequences of being conceived a twin, are determined in early gestation. Twin pregnancies in sheep were randomised to reduction of one twin on day 42 of a 148 day pregnancy by intra-thoracic KCl (Reductions, n =46) or a sham procedure (Twins, n =22). Singleton-bearing ewes also underwent a sham procedure (n =27). Ewes lambed spontaneously. Linear measures of size at birth were similar in Twins and Reductions, and significantly less than in Singletons. Birthweight was lower in Twins and Reductions than in Singletons, and less in Twins than in Reductions (means (SEM): Singletons, liveborn n =23: 6.59 (0.17) kg; Twins, liveborn n =36: 5.23 (0.16) kg; Reductions, liveborn n =27: 5.76 (0.15) kg; all comparisons P <0.05). Reductions grew most rapidly between birth and weaning (Singletons, 20.0 (0.4) g kg⁻¹ day⁻¹; Twins, 20.0 (0.3) g kg⁻¹ day⁻¹; Reductions, 21.0 (0.3) g kg⁻¹ day⁻¹, P <0.05) and were of similar weight as Singletons by weaning; Twins remained smaller by weaning but grew most rapidly thereafter (Singletons, 1.6 (0.1) g kg⁻¹ day⁻¹; Twins, 2.1 (0.1) g kg⁻¹ day⁻¹; Reductions, 1.6 (0.1) g kg⁻¹ day⁻¹, P <0.01), so that all groups had similar weight at 2 years. However, Twins and Reductions had greater percentage fat mass than Singletons at 2 years (Singletons, 11.1 (1.1)%; Twins, 14.8 (1.2)%; Reductions, 15.5 (1.1)%, P <0.05). Thus, in twins, fetal growth trajectory, linear size at birth and adult fat mass are largely determined in early gestation. If this is also true in humans, there are important implications for interventions aimed at optimising fetal growth and pregnancy outcome.

Periconceptional undernutrition suppresses cortisol response to arginine vasopressin and corticotropin-releasing hormone challenge in adult sheep offspring.

Poor maternal nutrition during pregnancy can result in increased disease risk in adult offspring. Many of these effects are proposed to be mediated via altered hypothalamo-pituitary-adrenal axis (HPAA) function, and are sex and age specific. Maternal undernutrition around the time of conception alters HPAA function in foetal and early postnatal life, but there are limited conflicting data about later effects. The aim of this study was to investigate the effect of moderate periconceptional undernutrition on HPAA function of offspring of both sexes longitudinally, from juvenile to adult life. Ewes were undernourished from 61 days before until 30 days after conception or fed ad libitum. HPAA function in offspring was assessed by arginine vasopressin plus corticotropin-releasing hormone challenge at 4, 10 and 18 months. Plasma cortisol response was lower in males than in females, and was not different between singles and twins. Periconceptional undernutrition suppressed offspring plasma cortisol but not adrenocorticotropic hormone responses. In males, this suppression was apparent by 4 months, and was more profound by 10 months, with no further change by 18 months. In females, suppression was first observed at 10 months and became more profound by 18 months. Maternal undernutrition limited to the periconceptional period has a prolonged, sex-dependent effect on adrenal function in the offspring.

Pregnancy and neonatal outcomes following hyperemesis gravidarum.

Undernutrition during pregnancy is associated with detrimental pregnancy and neonatal outcomes, which can have long-term implications for the infant. Hyperemesis gravidarum may severely limit nutritional intake. The aim of this study was to investigate the effect of hyperemesis on pregnancy and neonatal outcome, particularly gestation length and infant size at birth. Seventy-five prospectively recruited women admitted to a tertiary level hospital in Auckland, with hyperemesis gravidarum between March 2003 and October 2005, were compared to 142 controls matched for age, parity, ethnicity and expected date of delivery. Data were obtained from electronic records and analysed by Student's t-test, χ2, Wilcoxon, Fisher's exact tests and linear regression. Length of gestation, birth weight and crown-heel length were not different between participants and controls. Infants born to women with hyperemesis gravidarum had smaller head circumferences (Z-score mean (s.d.) 0.02 (0.16) v. 0.43 (0.11), P = 0.04 in all infants and -0.02 (1.24) v. 0.48 (1.29), P = 0.01 in-term infants). This study found hyperemesis gravidarum to be associated with smaller head circumferences in offspring. Given the reported associations between smaller head circumference at birth and lower cognitive ability and higher risk of cardiovascular disease in later life, further study is necessary to confirm these results and to determine whether there are any long-term implications for the offspring.

Effects of sex, litter size and periconceptional ewe nutrition on offspring behavioural and physiological response to isolation.

Maternal periconceptional undernutrition alters fetal hypothalamic-pituitary-adrenal (HPA) axis development. However, the effects of this early nutritional insult on postnatal HPA axis function and stress-related behaviours are unknown. We investigated in sheep the effects of different periods of undernutrition, and of sex and litter size, on offspring behavioural and cortisol responses to isolation stress. We studied four nutritional groups: controls well nourished throughout pregnancy (n=39), or ewes undernourished (UN, 10-15% body weight reduction) before mating (-60 to 0d, n=26), after mating (-2 to +30d, n=20) or both (-60 to +30d, n=36). At 4 and 18months of age, offspring were isolated for 5min, their behaviour video recorded, and plasma cortisol concentrations measured. Offspring of all undernourished groups demonstrated 50% fewer escape attempts than controls at 4 months of age, and offspring of UN-60+30 ewes had 20% lower plasma cortisol area under the curve in response to isolation at 18months. Females had higher cortisol concentrations and vocalised more than males at 4 and 18months, and were more active at 18months. After isolation, UN-2+30 males had higher cortisol concentrations than UN-2+30 females whereas in all other groups males had lower concentrations than females. Singleton males made more escape attempts than females, whereas in twins females made more escape attempts than males. These findings suggest that maternal periconceptional undernutrition in sheep can suppress behavioural reactions and cortisol secretion in response to isolation stress in the offspring into adulthood, and that these effects differ between males and females.