Association between adverse maternal and embryo-fetal effects in norfloxacin-treated and food-deprived rabbits

Effects of feed restriction during organogenesis on embryo-fetal development in rabbit

“…Maternal gestational body weight gain was impaired in all feed restricted groups, although only at feed levels of ≤55 g/day was there a decrease in mean maternal body weight, and it was necessary to restrict feed to 15 g/day to produce a net body weight loss during the feed restriction period. These maternal body weight effects were less severe than other reports that showed body weight loss at feed levels of 75 and 50 g/day (Clark et al, 1986; Petrere et al, 1993).…”

“…There were no fetal malformations associated with feed restriction. The literature to date contains conflicting reports about the relationship between feed restriction and abortion, fetal viability, malformations, and ossification delays; only two of these studies carried out thorough fetal evaluations (Clark et al, 1986; Matsuzawa et al, 1981; Perkin et al, 1984; Petrere et al, 1993). The results of the current evaluation, in context with previous reports, provide a clear picture of the impact that reduced feed consumption, and subsequent reductions in maternal gestational body weight gain, could have on developmental toxicology investigations.…”

“…Generally, this means sufficient exposure to reduce maternal food intake or reduce body weight gain so that by the end of the study the high dose animals weigh significantly less than controls. Given the relationship between maternal gestational body weight gain and healthy in utero development, and the regulatory guidance that maternal toxicity be demonstrated in non‐clinical studies, it is not surprising that much effort has been spent to determine the effects of reduced maternal body weight during pregnancy on fetal outcome (Lederman and Rosso, 1981; Matsuzawa et al, 1981; Clark et al, 1986; Petrere et al, 1993). Understanding the relationship between maternal body weight gain during pregnancy and prenatal development in non‐clinical studies becomes even more important when the pharmacology of the drug under evaluation is intended to promote weight loss.…”

Models of Intrauterine growth restriction and fetal programming in rabbits

“…In rabbits, maternal food restriction can also influence offspring outcomes, although the specific change depends on the timing, severity of the deprivation, and the resultant impacts on maternal body weight gain (summarized in Table ). In particular, ≤50% reduction in daily feed intake from early in gestation typically limits rabbit doe gestational weight gain and results in miscarriage, asymmetric IUGR, and fetal malformations, such as reduced bone ossification (Cappon, Fleeman, Chapin, & Hurtt, ; Clark et al, ; Flake, Villa, Adzick, & Harrison, ; López‐Tello et al, ; López‐Tello, Arias‐Álvarez, Jiménez‐Martínez, Barbero‐Fernández et al, ; López‐Tello, Arias‐Álvarez, Jimenez‐Martinez, Garcia‐Garciaet al, ; Matsuzawa, Nakata, Goto, & Tsushima, ; Petrere, ; Symeon et al, ). Offspring bone development is also impaired by malnutrition in other animal species, including rats that are exposed to a maternal low protein diet during gestation (Hanson & Gluckman, ; Hastings‐Roberts & Zeman, ; Wood, Stenson, & Embleton, ).…”

The effects of feed restriction during organogenesis on embryo-fetal development in the rat

“…Given the relationship between maternal body weight gain and healthy in utero development, and the regulatory guidance that maternal toxicity be demonstrated in non‐clinical studies (commonly exhibited by altered maternal body weight gain during pregnancy), it is not surprising that much effort has been spent to determine the effects of reduced maternal body weight gain during pregnancy on fetal outcome. While multiple studies consistent with regulatory testing paradigms have been conducted in the rabbit (Clark et al, 1986; Matsuzawa et al, 1981; Petrere et al, 1993), few data were available in the rat following regulatory study designs. Understanding the relationship between maternal body weight gain during pregnancy and prenatal development in non‐clinical studies becomes even more important when the drug under evaluation is intended to promote weight loss.…”