The blurring boundaries between placental and maternal preeclampsia: a critical appraisal of 1800 consecutive preeclamptic cases.

OBJECTIVES: To present a comprehensive overview of different risk factors for early onset preeclampsia (<34 weeks gestation, EOP) vs. late onset (LOP). STUDY DESIGN: South-Reunion University's maternity (Reunion Island, Indian Ocean). 18.5 year-observational population-based cohort study (2001-2019). Epidemiological perinatal database with information on obstetrical and neonatal risk factors. All consecutive singleton pregnancies (>21 weeks) compared with all preeclamptic pregnancies delivered in the south of Reunion island. MAIN OUTCOME MEASURES: Comparing risk factors between EOP and LOP. RESULTS: Among 1814 singleton preeclamptic pregnancies (600 EOP and 1214 LOP), EOP women were older than LOP 29.5 vs. 28.6 years, p = .009, primigravidas (OR 0.78 [0.63-0.96], p = .02) were prone to LOP. History of preeclampsia (PE) (aOR 12.8 vs. 7.1), chronic hypertension (aOR 6.5 vs. 4.5) had much higher adjusted odds ratios for EOP than for LOP, p < .001. Specific to EOP: coagulopathies (aOR 2.95, p = .04), stimulated pregnancies (aOR 3.9, p = .02). Specific to LOP: renal diseases (aOR 2.0, p = .05) and protective effect for smoking (aOR 0.75, p = .008). EOP women were prone to have a lower BMI. CONCLUSION: "Placental preeclampsia" (defective placentation) being linked to early onset PE (<34 weeks gestation) while "maternal preeclampsia" (maternal cardiovascular predisposition) being typically manifesting as the late form of the disease LOP is not systematically verified. Future researches are needed to propose a more adapted paradigm.Highlights  Risk factors for different preeclampsia phenotypes (early/late); challenging proposed models.

Ethnic differences in postmaturity syndrome in newborns. Reflections on different durations of gestation.

OBJECTIVE: To describe the prevalence, by weeks of gestation, of post-maturity signs in newborns by ethnic origins. STUDY DESIGN: Observational cohort study (2001-2018), of all consecutive singleton births delivered at Center Hospitalier Universitaire Hospitalier Sud Reunion's maternity (Reunion Island, French overseas department, Indian Ocean). The presence of clinical post-maturity signs was recorded by a week of gestation using Clifford's clinical post-maturity signs in newborns (desquamation, dry skin, wrinkling fingers and cracked skin). RESULTS: Of the 67,463 singleton births during the period, 58,503 newborns were from Reunion island, 5756 were of European origin (mainland France), and 4061 newborns from the archipelago of Comoros (North of Madagascar). Mean duration of gestation was 276 days in Caucasian women, 272 days in Comorian mothers and 273 days in Reunionese (p < .001). Post-maturity is defined by WHO as gestation greater than 293 days (41 weeks + 6 days). At 41 weeks (287 days) 12.1% of Caucasian babies presented post-maturity signs and 22.4% meconium-stained liquid versus respectively, 22.8 and 27.1% in Reunionese and 44 and 39.8% in Comorians (p < .001). CONCLUSION: Among African (Black) pregnancies, duration of gestation was approximately 7 days shorter than in Caucasian (White) pregnancies. In the Reunionese intermixed population and Comorians, the gestation was shorter by 3-4 days. Black newborns presented severe clinical post-maturity signs beginning around 40 weeks and 4-6 days, while it was 1 week later in white infants. Consequences of these differences, with respect to clinical outcomes, are discussed.

Safety Aspects of a Randomized Clinical Trial of Maternal and Infant Vitamin D Supplementation by Feeding Type Through 7 Months Postpartum.

Background: The safety of higher dose vitamin D (vitD) supplementation in women who change from exclusive or full breastfeeding to combination feeding or who continue supplementation after cessation of breastfeeding is unknown. Objective: Compare vitD supplementation safety of 6,400 to 400 IU/day and 2,400 IU/day using specific laboratory parameters in postpartum women and their infants through 7 months postpartum by feeding type. Design: In this randomized controlled trial, mothers (exclusively breastfeeding or formula-feeding) were randomized at 4-6 weeks' postpartum to 400, 2,400, or 6,400 IU vitD3 (cholecalciferol)/day for 6 months. Breastfeeding infants in 400 IU group received oral 400 IU vitD3/day; infants in 2,400 and 6,400 IU groups received placebo. Maternal safety parameters (serum vitD, 25-hydroxy-vitamin D [25(OH)D; calcidiol], calcium, phosphorus, intact PTH; urinary calcium/creatinine ratios; and feeding type/changes) were measured monthly; infant parameters were measured at months 1, 4, and 7. Sufficiency was defined as 25(OH)D >50 nmol/L. Feeding type was defined as exclusive/full, combination, or formula-feeding. Data were analyzed using SAS 9.4. Results: Four hundred nineteen mother-infant pairs were randomized into the three treatment groups and followed: 346 breastfeeding and 73 formula-feeding pairs. A dose of 6400 IU/day safely and significantly increased maternal vitD and 25(OH)D from baseline in all mothers regardless of feeding type (p < 0.0001) and was superior to the 400 and 2,400 IU groups in achieving vitD sufficiency with no other differences in safety parameters by treatment or feeding type. Infants in the 2,400 IU group were more likely vitD-deficient than the other groups; otherwise, there were no infant safety parameter differences. Conclusions: While 6,400 IU/day was more effective than 400 or 2,400 IU/day in achieving maternal vitD sufficiency in all feeding groups, the groups did not differ on other safety parameters. Similarly, infant safety parameters did not differ by treatment group or feeding status. Clinical Trial Registration: FDA IND Number: 66,346; ClinicalTrials.gov Number: NCT00412074.

Validation of the 34-week gestation as definition of late onset preeclampsia: Testing different cutoffs from 30 to 37 weeks on a population-based cohort of 1700 preeclamptics.

INTRODUCTION: Early onset preeclampsia (EOP) and late onset preeclampsia (LOP) have been differentiated with a cut-point of ≤34 weeks. This classical definition has never been examined with respect to maternal characteristics by different gestational age cut-points. We examined maternal characteristics in a population-based cohort of 1736 preeclamptic deliveries at different gestational age cut-points from 30 to 37 weeks (CO30 to CO37). MATERIAL AND METHODS: Eighteen-year observational population-based historical cohort study (2001-2018). All consecutive births delivered at the Centre Hospitalier Universitaire Hospitalier Sud Reunion's maternity. Standardized epidemiological perinatal database. RESULTS: The incidence of EOP was lower in adolescents (1.8% vs 3.5%, odds ratio [OR] 0.50, P = .17). Conversely, the odds of LOP was increased for women over 35, beginning at C030 (OR 1.13, P = .02) and this effect (OR = 1.2) was still detectable at C037 (P = .06). Among primigravid women, the incidence of EOP was lower than LOP (OR ranging from 0.71 to 0.82 for different CO). Conversely, the incidence of LOP was higher (adjusted OR about 2.7 [CO30-CO34] with a rise to 3.3 at CO37 (P < .001). Women with EOP had a lower body mass index (BMI) as compared with LOP at CO34 and CO37. The adjusted OR (per 5 kg/m2 increment) declined from 1.06 to 1.03 from CO30 to C037 in EOP women. Conversely, for LOP, the adjusted odds ratio (aOR) increased from 1.04 to 1.06 from CO30 to CO37 (P < .001). Gestational diabetes mellitus was not associated with LOP at any cut-off (aOR 1.07, NS) but was protective against EOP from CO30 to CO34 (aOR 0.42, 0.61 and 0.73, respectively, P < .001). This protective effect disappeared at CO37. Chronic hypertension and history of preeclampsia were both EOP and LOP risks but with a much stronger effect for EOP (chronic hypertension: aOR 6.0-6.5, history of preeclampsia: aOR 12-17). CONCLUSIONS: The 34th week of gestation appears to provide a reasonable cut-point to differentiate between EOP and LOP. Additional research is needed to better describe the possible differences in the pathophysiology of these different phenotypes.

Increased BMI has a linear association with late-onset preeclampsia: A population-based study.

BACKGROUND: To investigate the ongoing controversy on the effect of BMI (body mass index) on EOP (early onset preeclampsia) vs LOP (late onset), especially focusing on diabetes and maternal booking/pre-pregnancy BMI as possible independent variables. METHODS: 18 year-observational cohort study (2001-2018). The study population consisted of all consecutive births delivered at the Centre Hospitalier Universitaire Hospitalier Sud Reunion's maternity (ap. 4,300 birth per year, only level 3 maternity in the south of Reunion Island, sole allowed to follow and deliver all preeclampsia cases of the area). History of pregnancies, deliveries and neonatal outcomes have been collected in standardized fashion into an epidemiological perinatal data base. RESULTS: Chronic hypertension and, history of preeclampsia in multigravidas, were the strongest risk factors for EOP. Primiparity, age over 35 years and BMI ≥ 35 kg/m² were rather associated with LOP. In a multivariate analysis with EOP or LOP as outcome variables compared with controls (normotensive), maternal age and pre-pregnancy BMI were independent risk factors for both EOP and LOP (p < 0.001). However, analyzing by increment of 5 (years of age, kg/m² for BMI) rising maternal ages and incidence of preeclampsia were strictly parallel for EOP and LOP, while increment of BMI was only associated with LOP. Controlling for maternal ages and booking/pre-pregnancy BMI, diabetes was not an independent risk factor neither for EOP or LOP. CONCLUSIONS: Metabolic factors, other than diabetes, associated with pre-pregnancy maternal corpulence are specifically associated with LOP. This may be a direction for future researches on the maternal preeclamptic syndrome. This may explain the discrepancy we are facing nowadays where high-income countries report 90% of their preeclampsia being LOP, while it is only 60-70% in medium-low income countries.

Preeclampsia and the 20th century: "Le siècle des Lumières".

The authors delineate seven quantum leap forward and, or revolutions having occurred during the 20th century in the understanding of the physiopathology of preeclampsia. First the discovery of the inflatable arm band permitting to measure blood pressure in 1896. Second, the discovery that eclamptic (convulsions), and later "pre"eclamptic (proteinuria) women presented hypertension in 1897 and confirmed in 1903, discovery of the hypertensive disorders of pregnancy. Third, the eight major textbooks published all along the 20th century by delineating risk factors of preeclampsia with the concept of "preeclampsia, disease of primigravidae". Fourth, the discovery in the 1970's that human trophoblast implantation was far deeper than in other mammalian species. Fifth, and a major step forward, description at the end of the 1980's that the maternal syndrome in preeclampsia (glomeruloendotheliosis, HELLP syndrome, eclampsia) could be unified in a global endothelial cell inflammation. Sixth, the epidemiological descriptions in the 1970-1990's that indeed preeclampsia was a disease of first pregnancies at the level of a couple ("primipaternity concept"), leading to an explosion in immunological research in the last decade, beginning in 1998. Seventh and finally, in the search for the "factor X" explaining the vascular inflammation in preeclamptic women (inositol phospho glycans P-type were described in 2000, while soluble Flt-1 and S-endoglins have been clearly predicted since 1997). The majority of the seeds or findings have been grounded or realized in the 20th century. Indeed, for preeclampsia, the 20th century has been le "Siècle des Lumières" (the Enlightments).

Relationship between pre-pregnancy maternal BMI and optimal weight gain in singleton pregnancies.

BACKGROUND: There is a peculiar phenomenon: two separate individuals (mother and foetus) have a mutually interactive dependency concerning their respective weight. Very thin mothers have a higher risk of small for gestational age (SGA) infants, and rarely give birth to a large for gestational age (LGA) infant. While morbidly obese women often give birth to LGA infants, and rarely to SGA. Normal birthweight (AGA) infants (>10th and <90th centile of a neonatal population) typically have the lowest perinatal and long-term morbidity. The aim of the current study is (1) to determine the maternal body mass index (BMI) range associated with a balanced risk (10% SGA, 10% LGA), and (2) to investigate the interaction between maternal booking BMI, gestational weight gain (GWG) and neonatal birthweight centiles. METHODS: 16.5 year-observational cohort study (2001-2017). The study population consisted of all consecutive singleton term (37 weeks onward) live births delivered at University's maternity in Reunion island, French Overseas Department. FINDINGS: Of the 59,717 singleton term live births, we could define the booking BMI and the GWG in 52,092 parturients (87.2%). We had 2 major findings (1) Only women with a normal BMI achieve an equilibrium in the SGA/LGA risk (both 10%). We propose to call this crossing point the Maternal Fetal Corpulence Symbiosis (MFCS). (2) This MFCS shifts with increasing GWG. We tested the MFCS by 5 kg/m2 incremental BMI categories. The result is a linear law:opGWG (kg) = -1.2 ppBMI (Kg/m²) + 42 ± 2 kg. INTERPRETATION: IOM-2009 recommendations are adequate for normal and over-weighted women but not for thin and obese women: a thin woman (17 kg/m2) should gain 21.6 ± 2 kg (instead of 12.5-18). An obese 32 kg/m2 should gain 3.6 kg (instead of 5-9). Very obese 40 kg/m2 should lose 6 kg.

A Retrospective Database Analysis of Neonatal Morbidities to Evaluate a Composite Endpoint for Use in Preterm Labor Clinical Trials.

Objective To propose and assess a composite endpoint (CE) of neonatal benefit based on neonatal mortality and morbidities by gestational age (GA) for use in preterm labor clinical trials. Study Design A descriptive, retrospective analysis of the Medical University of South Carolina Perinatal Information System database was conducted. Neonatal morbidities were assessed for inclusion in the CE based on clinical significance/risk of childhood neurodevelopmental impairment, frequency, and association with GA in a mother-neonate linked cohort, comprising women with uncomplicated singleton pregnancies delivered at ≥24 weeks' GA. Results Among 17,912 mother-neonate pairs, neonates were at a risk of numerous severe but infrequent morbidities. Clinically important, predominantly rare events were combined into a CE comprising neonatal mortality and morbidities, which decreased in frequency with increasing GA. The highest CE frequency occurred at <31 weeks. High frequency of respiratory distress syndrome, bronchopulmonary dysplasia, and sepsis drove the CE. Median length of hospital stay was longer at all GAs in those with the CE compared with those without. Conclusions Descriptive epidemiological assessment and clinical input were used to develop a CE to measure neonatal benefit, comprising clinically meaningful outcomes. These empirical data and CE allowed trials investigating tocolytics to be sized appropriately.

Linear association between maternal age and spontaneous breech presentation in singleton pregnancies after 32 weeks gestation.

PURPOSE: To investigate the association between maternal age and spontaneous breech presentation. MATERIAL AND METHODS: Fifteen-year observational study over (2001-2015). All consecutive singleton births delivered at the Centre Hospitalier Universitaire Sud Reunion's maternity. The only single exclusion criterion was uterine malformations (N = 123) women. RESULTS: Of the 60,963 singleton births, there was a linear association (χ2 for linear trend, p< 0.0001) between maternal age and spontaneous breech presentation. Overall rate of breech presentation was 2.7% in deliveries over 32 weeks gestation, while it was 1.9% in women aged 15 to 19 years and 4.0% in women aged 45+, with a linear progression for each 5-year age category. This linearity remained significant controlling for early prematurity (<33 weeks) and severe fetal malformations (χ2 for linear trend = 64, p < 0.0001). Controlling in a multiple logistic regression model for other major risk factors gestational age, female sex, primiparity, maternal age remained significantly an independent risk factor, p < 0.0001. CONCLUSION: Maternal age (x) is an independent factor for breech presentation in singleton pregnancies after 32 weeks gestation with a linear association that may be approximated at y = 0.1x. (y: incidence, percent).

Linear association between maternal age and need of medical interventions at delivery in primiparae: a cohort of 21,235 singleton births.

OBJECTIVES: We sought to investigate the potential association between maternal age and the need for active obstetrical intervention intrapartum in primiparas. STUDY DESIGN: Observational study over 14 years (2001-2014) of all consecutive primiparous singleton births having delivered at the Centre Hospitalier Universitaire Hospitalier Sud Reunion's maternity (French overseas department, Indian Ocean). RESULTS: Of the 21,235 singleton primiparous births, there were three significant linear associations between maternal age from 12 years of age to 42 + (all χ2 for linear trend, p < .0001) (a) vaginal deliveries without any medical intervention, (b) rate of cesarean sections, and (c) rate of operative vaginal procedures. These three linear associations persisted when controlling for maternal obesity (±30 kg/m2), "heavy babies" (>3.5 kg), and ethnicity. Using maternal age remained significantly an independent risk factor (p < .0001), after controlling for the major confounders: maternal BMI, maternal height, birthweight ≥3500 g, p < .0001. CONCLUSIONS: Increasing maternal age has a linear association with vaginal deliveries without any medical intervention, rate of cesarean sections, and rate of operative vaginal procedures. These associations are independent of maternal BMI and maternal height. We currently do not have a specific explanation why younger women appear to be protected from requiring intrapartum obstetric intervention. Nevertheless, these strong facts deserve acknowledgement and further research.

Historical evolution of ideas on eclampsia/preeclampsia: A proposed optimistic view of preeclampsia.

Eclampsia (together with epilepsy) being the first disease ever written down since the beginning of writings in mankind 5000 years ago, we will make a brief presentation of the different major steps in comprehension of Pre-eclampsia. 1) 1840. Rayer, description of proteinuria in eclampsia, 2) 1897 Vaquez, discovery of gestational hypertension in eclamptic women, 3) In the 1970's, description of the "double" trophoblastic invasion existing only in humans (Brosens & Pijnenborg,), 4) between the 1970's and the 1990's, description of preeclampsia being a couple disease. The "paternity problem" (and therefore irruption of immunology), 5) at the end of the 1980's, a major step forward: Preeclampsia being a global endothelial cell disease (glomeruloendotheliosis, hepatic or cerebral endotheliosis, HELLP, eclampsia), inflammation (J.Roberts.C Redman, R Taylor), 6) End of the 1990's: Consensus for a distinction between early onset preeclampsia EOP and late onset LOP (34 weeks gestation), EOP being rather a problem of implantation of the trophoblast (and the placenta), LOP being rather a pre-existing maternal problem (obesity, diabetes, coagulopathies etc…). LOP is predominant everywhere on this planet, but enormously predominant in developed countries: 90% of cases. This feature is very different in countries where women have their first child very young (88% of world births), where the fatal EOP (early onset) occurs in more than 30% of cases. 7) What could be the common factor which could explain the maternal global endotheliosis in EOP and LOP? Discussion about the inositol phospho glycans P type.

Prenatal vitamin D and enamel hypoplasia in human primary maxillary central incisors: a pilot study.

BACKGROUND: Enamel hypoplasia (EH) increases risk for dental caries and also is associated with vitamin D deficiencies. This pilot study evaluates the feasibility to determine the association of human maternal circulating vitamin D concentrations during pregnancy and EH in infant's teeth that develop in utero. METHODS: A pilot population of 37 children whose mothers participated in a RCT of vitamin D supplementation during pregnancy was evaluated. Major outcome was EH and major exposure was maternal monthly serum circulating 25(OH)D concentrations during pregnancy. EH was assessed using the Enamel Defect Index and digital images made by a ProScope High Resolution™ handheld digital USB microscope at 50x magnification. RESULTS: During initial 8 weeks of study, 29/37 children had evaluable data with mean age of 3.6 ± 0.9 years; 48% male; and 45% White, 31% Hispanic, and 24% Black. EH was identified in 13 (45%) of the children. Maternal mean 25(OH)D concentrations were generally lower for those children with EH. CONCLUSIONS: Preliminary results suggest follow-up of children of mothers in a vitamin D supplementation RCT during pregnancy provides an important approach to study the etiology of EH in the primary teeth. Further study is needed to discern thresholds and timing of maternal serum 25(OH)D concentrations during pregnancy associated with absence of EH in teeth that develop in utero. Potential dental public health implications for prevention of early childhood caries via sound tooth structure as related to maternal vitamin D sufficiency during pregnancy need to be determined.

Evaluating the Potential Severity of Look-Alike, Sound-Alike Drug Substitution Errors in Children.

OBJECTIVE: Look-alike, sound-alike (LASA) drug name substitution errors in children may pose potentially severe consequences. Our objective was to determine the degree of potential harm pediatricians ascribe to specific ambulatory LASA drug substitution errors. METHODS: We developed a unified list of LASA pairs from published sources, removing selected drugs on the basis of preparation type (eg, injectable drugs). Using a modified Delphi method over 3 rounds, 38 practicing pediatricians estimated degree of potential harm that might occur should a patient receive the delivered drug in error and the degree of potential harm that might occur from not receiving the intended drug. RESULTS: We identified 3550 published LASA drug pairs. A total of 1834 pairs were retained for the Delphi surveys, and 608 drug pairs were retained for round 3. Final scoring demonstrated that participants were able to identify pairs where the substitutions represented high risk of harm for receiving the delivered drug in error (eg, did not receive methylphenidate/received methadone), high risk of harm for not receiving the intended drug (eg, did not receive furosemide/received fosinopril), and pairs where the potential harm was high from not receiving the intended drug and from erroneously receiving the delivered drug (eg, did not receive albuterol/received labetalol). CONCLUSIONS: Pediatricians have identified LASA drug substitutions that pose a high potential risk of harm to children. These results will allow future efforts to prioritize pediatric LASA errors that can be screened prospectively in outpatient pharmacies.

Potential Unintended Consequences of a Conservative Management Strategy for Patent Ductus Arteriosus.

BACKGROUND: A recent review supports a strategy of deferring treatment of patent ductus arteriosus (PDA) in the preterm neonate until at least the second week after birth. In light of previous suggestion that later initiation of treatment may be less efficacious for closing PDAs it is reasonable to question if delayed treatment may be less effective. DESIGN: We conducted a single center retrospective review of a neonatal intensive care unit database of infants ≤37 weeks gestation with the diagnosis of PDA and treated with indomethacin from 1999 to 2007. We determined gestational age (GA), timing of indomethacin initiation, and status of the PDA at hospital discharge. Treatment failure was defined as neonates requiring further intervention to close their PDA or those who died without echo-proven PDA closure. RESULTS: Of the 341 infants meeting the study criteria, 77 (23%) had defined treatment failure. The failure group had a younger median GA of 25 weeks (interquartile range [IQR], 24-26) vs. 28 weeks (IQR, 26-30) for the successful group (P < .0001). The failure group had a median treatment initiation on day of life (DOL) 4 (IQR, 1-8) compared with DOL 3 (IQR, 1-6) for those in the successful group (P = .15). Taken as a whole, infants treated after DOL 5 were significantly more likely to have treatment failure (30.1% vs. 19.3% for those treated DOL 1-5, P = .03). CONCLUSIONS: Our study confirms that younger GA at birth is correlated with increased likelihood of failed PDA closure. We also show a trend indicating that later initiation of treatment may decrease the chances of successfully closing a PDA. Future examination of PDA management should consider the potential unintended consequences that may accompany a delayed treatment strategy.

The efficacy assessment of a self-administered immunotherapy protocol.

BACKGROUND: We previously reported the safety of a self-administered subcutaneous immunotherapy (SCIT) protocol. Here we report the results of the retrospective efficacy trial of the United Allergy Service (UAS) self-administered SCIT protocol. We hypothesized that by utilizing a slow SCIT buildup phase, designed to attain recommended allergen concentrations on a cumulative basis, efficacious outcomes and clinical relevance would be achieved. METHODS: We enrolled 60 SCIT patients and 56 control patients. The study contrasted baseline and treatment period combined symptom plus medication scores (CSMS) as the primary outcome measure and rhinoconjunctivitis quality of life questionnaire (RQLQ) scores as the secondary study outcome measure. Changes in pollen counts were also examined with regard to effects on these efficacy parameters. RESULTS: The treatment group showed significantly improved CSMS (standardized mean difference [SMD]: -1.57; 95% confidence interval [CI], -1.97 to -1.18; p < 0.001) and RQLQ (SMD: -0.91; 95% CI, -1.23 to -0.59; p < 0.001). These treatment group outcome measures were respectively improved by 33% and 29% compared to baseline and greater than 40% in comparison to the control group (p < 0.0001). Significant results were also shown when examining these outcome measures with regards to either monotherapy or poly-allergen SCIT. Furthermore, a comparison to recent meta-analyses of SCIT studies showed equivalent efficacy and clinical relevance. Assessment of pollen counts during the baseline and treatment periods further corroborated the efficacy of the UAS SCIT protocol. CONCLUSION: These efficacy results, and our previous safety results, show that a carefully designed and implemented self-administered SCIT protocol is efficacious and safe.

Potential Acetaminophen and Opioid Overdoses in Young Children Prescribed Combination Acetaminophen/Opioid Preparations.

INTRODUCTION: Combination preparations of acetaminophen/opioid are the most common opioid form prescribed to children. We tested the hypothesis that dispensed prescriptions of acetaminophen/opioid preparations more appropriately match acetaminophen dosing parameters than opioid dosing parameters. We also hypothesized that the frequency of potential overdose was inversely related to subject age. METHODS: Using 2011 to 2012 South Carolina outpatient Medicaid data, the authors identified acetaminophen/opioid preparations dispensed to children 0 to 36 months. Utilizing Centers for Disease Control and Prevention (CDC) data to impute subject weights as the 97th percentile for age and gender, the authors used imputed weights to calculate the maximum recommended daily dose (expected dose) of each component. We calculated the dose delivered per day (observed dose) based on drug concentration, volume dispensed, and days' supply and then calculated the frequency of overdose (observed dose/expected dose, >1.10) by each component, comparing overdose frequency of acetaminophen to the overdose frequency of opioid using a risk ratio. Logistic regression evaluated differences in potential overdose by age, controlling for race/ethnicity and gender. RESULTS: Among 2,653 dispensed prescriptions of study drugs to 2,308 children 0 to 36 months old, the frequency of potential overdose was 0.7% for acetaminophen and 1.6% for opioid (risk ratio, 2.28). Age less than 3 months was associated with a greater frequency of potential overdose of either acetaminophen or opioid, even after controlling for gender and race/ethnicity. CONCLUSIONS: Prescriptions of acetaminophen-opioid drugs dispensed to children 0 to 36 months old contained potential overdoses of opioid at greater than twice the frequency of acetaminophen and were more likely to occur in infants less than 3 months old.

Maternal Versus Infant Vitamin D Supplementation During Lactation: A Randomized Controlled Trial.

OBJECTIVE: Compare effectiveness of maternal vitamin D3 supplementation with 6400 IU per day alone to maternal and infant supplementation with 400 IU per day. METHODS: Exclusively lactating women living in Charleston, SC, or Rochester, NY, at 4 to 6 weeks postpartum were randomized to either 400, 2400, or 6400 IU vitamin D3/day for 6 months. Breastfeeding infants in 400 IU group received oral 400 IU vitamin D3/day; infants in 2400 and 6400 IU groups received 0 IU/day (placebo). Vitamin D deficiency was defined as 25-hydroxy-vitamin D (25(OH)D) <50 nmol/L. 2400 IU group ended in 2009 as greater infant deficiency occurred. Maternal serum vitamin D, 25(OH)D, calcium, and phosphorus concentrations and urinary calcium/creatinine ratios were measured at baseline then monthly, and infant blood parameters were measured at baseline and months 4 and 7. RESULTS: Of the 334 mother-infant pairs in 400 IU and 6400 IU groups at enrollment, 216 (64.7%) were still breastfeeding at visit 1; 148 (44.3%) continued full breastfeeding to 4 months and 95 (28.4%) to 7 months. Vitamin D deficiency in breastfeeding infants was greatly affected by race. Compared with 400 IU vitamin D3 per day, 6400 IU/day safely and significantly increased maternal vitamin D and 25(OH)D from baseline (P < .0001). Compared with breastfeeding infant 25(OH)D in the 400 IU group receiving supplement, infants in the 6400 IU group whose mothers only received supplement did not differ. CONCLUSIONS: Maternal vitamin D supplementation with 6400 IU/day safely supplies breast milk with adequate vitamin D to satisfy her nursing infant's requirement and offers an alternate strategy to direct infant supplementation.

Opioid Prescribing and Potential Overdose Errors Among Children 0 to 36 Months Old.

OBJECTIVE: To estimate the frequency of potential overdoses among outpatient opioid-containing prescriptions. METHOD: Using 11 years of outpatient Medicaid prescription data, we compared opioid dose dispensed (observed) versus expected dose to estimate overdose error frequencies. A potential overdose was defined as any preparation dispensed that was >110% of expected based on imputed, 97th percentile weights. RESULTS: There were 59 536 study drug prescriptions to children 0 to 36 months old. Overall, 2.7% of the prescriptions contained potential overdose quantities, and the average excess amount dispensed was 48% above expected. Younger ages were associated with higher frequencies of potential overdose. For example, 8.9% of opioid prescriptions among infants 0 to 2 months contained potential overdose quantities, compared with 5.7% among infants 3 to 5 months old, 3.6% among infants 6 to 11 months old, and 2.3% among children >12 months (P < .0001). CONCLUSIONS: Opioid prescriptions for infants and children routinely contained potential overdose quantities.

Diagnostic accuracy of fundal height and handheld ultrasound-measured abdominal circumference to screen for fetal growth abnormalities.

OBJECTIVE: We sought to compare fundal height and handheld ultrasound-measured fetal abdominal circumference (HHAC) for the prediction of fetal growth restriction (FGR) or large for gestational age. STUDY DESIGN: This was a diagnostic accuracy study in nonanomalous singleton pregnancies between 24 and 40 weeks' gestation. Patients underwent HHAC and fundal height measurement prior to formal growth ultrasound. FGR was defined as estimated fetal weight less than 10%, whereas large for gestational age was defined as estimated fetal weight greater than 90%. Sensitivity and specificity were calculated and compared using methods described elsewhere. RESULTS: There were 251 patients included in this study. HHAC had superior sensitivity and specificity for the detection of FGR (sensitivity, 100% vs 42.86%) and (specificity, 92.62% vs 85.24%). HHAC had higher specificity but lower sensitivity when screening for LGA (specificity, 85.66% vs 66.39%) and (sensitivity, 57.14% vs 71.43%). CONCLUSION: HHAC could prove to be a valuable screening tool in the detection of FGR. Further studies are needed in a larger population.