Trecia A. Wouldes

Metformin in Gestational Diabetes: The Offspring Follow-Up (MiG TOFU): Body composition at 2 years of age

OBJECTIVE In women with gestational diabetes mellitus, who were randomized to metformin or insulin treatment, pregnancy outcomes were similar (Metformin in Gestational diabetes [MiG] trial). Metformin crosses the placenta, so it is important to assess potential effects on growth of the children. RESEARCH DESIGN AND METHODS In Auckland, New Zealand, and Adelaide, Australia, women who had participated in the MiG trial were reviewed when their children were 2 years old. Body composition was measured in 154 and 164 children whose mothers had been randomized to metformin and insulin, respectively. Children were assessed with anthropometry, bioimpedance, and dual energy X-ray absorptiometry (DEXA), using standard methods. RESULTS The children were similar for baseline maternal characteristics and pregnancy outcomes. In the metformin group, compared with the insulin group, children had larger mid-upper arm circumferences (17.2 ± 1.5 vs. 16.7 ± 1.5 cm; P = 0.002) and subscapular (6.3 ± 1.9 vs. 6.0 ± 1.7 mm; P = 0.02) and biceps skinfolds (6.03 ± 1.9 vs. 5.6 ± 1.7 mm; P = 0.04). Total fat mass and percentage body fat assessed by bioimpedance (n = 221) and DEXA (n = 114) were not different. CONCLUSIONS Children exposed to metformin had larger measures of subcutaneous fat, but overall body fat was the same as in children whose mothers were treated with insulin alone. Further follow-up is required to examine whether these findings persist into later life and whether children exposed to metformin will develop less visceral fat and be more insulin sensitive. If so, this would have significant implications for the current pandemic of diabetes.

Depression in Older People: Visual Impairment and Subjective Ratings of Health

Purpose. The aim of this study was to establish the prevalence of depression in a sample of older adults with impaired vision and investigate associations between physical and visual disability and depression. Methods. We analyzed cross-sectional baseline data from 391 participants aged ≥75 years with visual acuity of 6/24 (20/80) or less, recruited for a randomized controlled trial of interventions to prevent falls (the VIP trial). Measures included the geriatric depression scale (GDS-15), the state-trait anxiety index, activities of daily living (Nottingham extended ADL scale), physical activity (human activity profile), an index of visual functioning (VF-14), health-related quality of life (SF-36), objective measures of physical ability, and a measure of visual acuity. Regression models were developed to investigate the association between depression scores and physical, psychological, and visual disability. Results. About 29.4% (115 of 391) of participants were identified as potentially depressed (GDS-15 score >4). Physical function, physical activity, physical ability, visual function, anxiety, and self-reported physical and mental health were significantly worse for those with depressive symptomatology. Physical, visual, and psychological factors collectively explained 41% of the variance in the depression score in a linear regression model (R2 = 0.421, adjusted R2 = 0.410, F (7,382) = 39.680, p < 0.001). Depression was not related to age, gender, living situation, ethnicity, or number of prescription or antidepressant medications taken. Conclusions. Depression was common in this population of older adults with severe visual impairment. Impaired visual and physical functions were associated with symptoms of depression. The effect of visual disability was independent of the effect of physical disability. The strength of this relationship, and the results of the regression analyses, indicate that a person who is visually or physically disabled is more likely to suffer from depression.

Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years

BACKGROUND Neonatal hypoglycemia is common and can cause neurologic impairment, but evidence supporting thresholds for intervention is limited. METHODS We performed a prospective cohort study involving 528 neonates with a gestational age of at least 35 weeks who were considered to be at risk for hypoglycemia; all were treated to maintain a blood glucose concentration of at least 47 mg per deciliter (2.6 mmol per liter). We intermittently measured blood glucose for up to 7 days. We continuously monitored interstitial glucose concentrations, which were masked to clinical staff. Assessment at 2 years included Bayley Scales of Infant Development III and tests of executive and visual function. RESULTS Of 614 children, 528 were eligible, and 404 (77% of eligible children) were assessed; 216 children (53%) had neonatal hypoglycemia (blood glucose concentration, <47 mg per deciliter). Hypoglycemia, when treated to maintain a blood glucose concentration of at least 47 mg per deciliter, was not associated with an increased risk of the primary outcomes of neurosensory impairment (risk ratio, 0.95; 95% confidence interval [CI], 0.75 to 1.20; P=0.67) and processing difficulty, defined as an executive-function score or motion coherence threshold that was more than 1.5 SD from the mean (risk ratio, 0.92; 95% CI, 0.56 to 1.51; P=0.74). Risks were not increased among children with unrecognized hypoglycemia (a low interstitial glucose concentration only). The lowest blood glucose concentration, number of hypoglycemic episodes and events, and negative interstitial increment (area above the interstitial glucose concentration curve and below 47 mg per deciliter) also did not predict the outcome. CONCLUSIONS In this cohort, neonatal hypoglycemia was not associated with an adverse neurologic outcome when treatment was provided to maintain a blood glucose concentration of at least 47 mg per deciliter. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.).

Risk factors for and prevention of human papillomaviruses (HPV), genital warts and cervical cancer

Genital HPV infection is associated with development of cervical cancer, cervical neoplasia, anogenital warts, and other anogenital cancers. A number of reviews have primarily addressed the role of HPV infection in cervical carcinogenesis, and differences in human papillomavirus (HPV) subtypes found in cervical cancer cases by histology and geographical region. This review provides an informative summary of the broad body of literature on the burden of HPV, the risk factors for HPV infection, genital warts and cervical cancer, and preventive measures against these conditions in females. Studies have identified the main risk factors for genital HPV infection in females as follows: acquisition of new male partners; an increasing number of lifetime sexual partners both in females and their male partners; and having non-monogamous male partners. Cervical cancer screening and HPV vaccination are the primary measures currently recommended to prevent cervical cancer. There is also an ongoing debate and conflicting findings on whether male circumcision and condom use protect against HPV infection and subsequent development of HPV-related illnesses in females.

Prenatal methamphetamine exposure and neonatal neurobehavioral outcome in the USA and New Zealand.

BACKGROUND Methamphetamine (MA) use among pregnant women is a world-wide problem, but little is known of its impact on exposed infants. DESIGN The prospective, controlled longitudinal Infant Development, Environment and Lifestyle (IDEAL) study of prenatal MA exposure from birth to 36 months was conducted in the US and NZ. The US cohort has 183 exposed and 196 comparison infants; the NZ cohort has 85 exposed and 95 comparison infants. Exposure was determined by self-report and meconium assay with alcohol, marijuana, and tobacco exposures present in both groups. The NICU Neurobehavior Scale (NNNS) was administered within 5 days of life. NNNS summary scores were analyzed for exposure including heavy exposure and frequency of use by trimester and dose-response relationship with the amphetamine analyte. RESULTS MA exposure was associated with poorer quality of movement, more total stress/abstinence, physiological stress, and CNS stress with more nonoptimal reflexes in NZ but not in the USA. Heavy MA exposure was associated with lower arousal and excitability. First trimester MA use predicted more stress and third trimester use more lethargy and hypotonicity. Dose-response effects were observed between amphetamine concentration in meconium and CNS stress. CONCLUSION Across cultures, prenatal MA exposure was associated with a similar neurobehavioral pattern of under arousal, low tone, poorer quality of movement and increased stress.

A qualitative study of filicide by mentally ill mothers

OBJECTIVE To examine descriptions of maternal filicide committed in the context of major mental illness from the frame of reference of a group of perpetrators. METHOD Participants were accessed via their treating psychiatrists. A naturalistic paradigm was used. Semi-structured individual interviews were audio-taped and transcribed. Theme analysis of the transcripts was done by repeated reading of transcripts and coding utterances, individually, then jointly by the authors. RESULTS Six women were identified, and interviewed. They described intense investment in mothering their child(ren). Descriptions of external stressors were not extreme, but the experience of illness was described as extremely stressful. They described little or no warning or planning. Their descriptions of their children were unremarkable. Motivation was described as altruistic or as an extension of suicide. They described regretting the killings and feeling responsible even though they knew they had been ill at the time. CONCLUSIONS The findings underline the difficulty of identification of risk and prevention of maternally ill filicide in the women who described being very caring towards their children, and little or no warning of filicidal urges. They may be better understood in terms of the illness than individual stress or psychodynamics.

Co-morbidity of substance use disorder and psychopathology in women who use methamphetamine during pregnancy in the US and New Zealand

BACKGROUND Methamphetamine (MA) abuse is a worldwide problem. Little is known about the co-morbidity of substance use disorders (SUD) and other psychiatric disorders of mothers who use MA prenatally. The Infant Development, Environment and Lifestyle (IDEAL) Study is a prospective, investigation of prenatal MA use and child outcome in the United States (US) and New Zealand (NZ). This study examined prenatal MA use and the co-morbidity of SUD and psychiatric disorders at 1-month postpartum. METHOD Mothers who used MA (US=127, NZ=97) were compared to a matched comparison group (US=193, NZ=110). The Substance Abuse Subtle Screening Inventory-3 was used to measure the probability of a SUD. The Brief Symptom Inventory (BSI) was used to measure the likelihood of a positive diagnosis of a psychiatric disorder. RESULTS In the US and NZ, MA groups had lower SES, increased single parenting, delayed prenatal care, and increased polydrug use. In the US only, MA mothers had lower income than the comparison group. MA users were 10 times more likely to have a SUD and twice as likely to meet BSI criteria for a diagnosable psychiatric disorder. In NZ, but not the US, MA users were five times more likely to have co-morbidity of both. This disparity may be due to higher quantities of prenatal alcohol use associated with increased psychiatric symptoms. CONCLUSION These findings suggest that addressing both substance abuse and psychiatric disorders in mothers who use MA may be required to effectively treat maternal MA use.

Neurodevelopmental and body composition outcomes in children with congenital hypothyroidism treated with high-dose initial replacement and close monitoring

BACKGROUND Despite newborn screening and early levothyroxine replacement, there are continued reports of mild neurocognitive impairment in children with congenital hypothyroidism (CHT). In Auckland, New Zealand, cases are identified by a neonatal screening program with rapid institution of high-dose levothyroxine replacement (10-15 μg/kg·d), producing prompt normalization of thyroid function. Subsequently, frequent monitoring and dose alterations are performed for 2 years. We aimed to assess whether the Auckland treatment strategy prevents impairment of intellectual and motor development. METHODS This study encompassed all children with CHT born in 1993-2006 in Auckland and their siblings. Neurocognitive assessments included the following: 1) intelligence quotient via Weschler Preschool and Primary Scale of Intelligence III or Weschler Intelligence Scale for Children IV; 2) Movement Assessment Battery for Children; and 3) Beery Developmental Test of Visual-Motor Integration. Body composition was assessed by dual-energy x-ray absorptiometry. RESULTS Forty-four CHT cases and 53 sibling controls aged 9.6 ± 3.9 years were studied. Overall intelligence quotient was similar among CHT cases and controls (95.2 vs 98.6; P = .20), and there were also no differences in motor function. Severity of CHT did not influence outcome, but greater time to normalize free T4 was associated with worse motor balance. There were no differences in anthropometry or body composition between groups. CONCLUSIONS These findings suggest that a strategy of rapidly identifying and treating infants with CHT using high-dose levothyroxine replacement is associated with normal intellectual and motor development. The subtle negative impact on motor function associated with time to normalize free T4 levels is consistent with benefit from rapid initial correction.

Association of Neonatal Glycemia With Neurodevelopmental Outcomes at 4.5 Years

Importance Hypoglycemia is common during neonatal transition and may cause permanent neurological impairment, but optimal intervention thresholds are unknown. Objective To test the hypothesis that neurodevelopment at 4.5 years is related to the severity and frequency of neonatal hypoglycemia. Design, Setting, and Participants The Children With Hypoglycemia and Their Later Development (CHYLD) Study is a prospective cohort investigation of moderate to late preterm and term infants born at risk of hypoglycemia. Clinicians were masked to neonatal interstitial glucose concentrations; outcome assessors were masked to neonatal glycemic status. The setting was a regional perinatal center in Hamilton, New Zealand. The study was conducted from December 2006 to November 2010. The dates of the follow-up were September 2011 to June 2015. Participants were 614 neonates born from 32 weeks’ gestation with at least 1 risk factor for hypoglycemia, including diabetic mother, preterm, small, large, or acute illness. Blood and masked interstitial glucose concentrations were measured for up to 7 days after birth. Infants with hypoglycemia (whole-blood glucose concentration <47 mg/dL) were treated to maintain blood glucose concentration of at least 47 mg/dL. Exposures Neonatal hypoglycemic episode, defined as at least 1 consecutive blood glucose concentration less than 47 mg/dL, a severe episode (<36 mg/dL), or recurrent (≥3 episodes). An interstitial episode was defined as an interstitial glucose concentration less than 47 mg/dL for at least 10 minutes. Main Outcomes and Measures Cognitive function, executive function, visual function, and motor function were assessed at 4.5 years. The primary outcome was neurosensory impairment, defined as poor performance in one or more domains. Results In total, 477 of 604 eligible children (79.0%) were assessed. Their mean (SD) age at the time of assessment was 4.5 (0.1) years, and 228 (47.8%) were female. Those exposed to neonatal hypoglycemia (280 [58.7%]) did not have increased risk of neurosensory impairment (risk difference [RD], 0.01; 95% CI, −0.07 to 0.10 and risk ratio [RR], 0.96; 95% CI, 0.77 to 1.21). However, hypoglycemia was associated with increased risk of low executive function (RD, 0.05; 95% CI, 0.01 to 0.10 and RR, 2.32; 95% CI, 1.17 to 4.59) and visual motor function (RD, 0.03; 95% CI, 0.01 to 0.06 and RR, 3.67; 95% CI, 1.15 to 11.69), with highest risk in children exposed to severe, recurrent, or clinically undetected (interstitial episodes only) hypoglycemia. Conclusions and Relevance Neonatal hypoglycemia was not associated with increased risk of combined neurosensory impairment at 4.5 years but was associated with a dose-dependent increased risk of poor executive function and visual motor function, even if not detected clinically, and may thus influence later learning. Randomized trials are needed to determine optimal screening and intervention thresholds based on assessment of neurodevelopment at least to school age.

Developmental and behavioral consequences of prenatal methamphetamine exposure: A review of the Infant Development, Environment, and Lifestyle (IDEAL) study

This study reviews the findings from the Infant Development, Environment, and Lifestyle (IDEAL) study, a multisite, longitudinal, prospective study designed to determine maternal outcome and child growth and developmental findings following prenatal methamphetamine exposure from birth up to age 7.5 years. These findings are presented in the context of the home environment and caregiver characteristics to determine how the drug and the environment interact to affect the outcome of these children. No neonatal abstinence syndrome requiring pharmacologic intervention was observed but heavy drug exposure was associated with increased stress responses in the neonatal period. Poorer inhibitory control was also observed in heavy methamphetamine exposed children placing them at high risk for impaired executive function. Independent of methamphetamine exposure, children with more responsive home environments to developmental and emotional needs demonstrated lower risks for internalizing and externalizing behavior.