Recombinant human prolactin for the treatment of lactation insufficiency

Abstract

Context: Lactation insufficiency has many aetiologies including complete or relative prolactin deficiency. Exogenous prolactin may increase breast milk volume in this subset. We hypothesized that recombinant human prolactin (r-hPRL) would increase milk volume in mothers with prolactin deficiency and mothers of preterm infants with lactation insufficiency.

Design: Study 1: R-hPRL was administered in an open-label trial to mothers with prolactin deficiency. Study 2: R-hPRL was administered in a randomized, double-blind, placebo-controlled trial to mothers with lactation insufficiency that developed while pumping breast milk for their preterm infants.

Patients: Study 1: Mothers with prolactin deficiency (n = 5). Study 2: Mothers of premature infants exclusively pumping breast milk (n = 11).

Design: Study 1: R-hPRL (60 μg/kg) was administered subcutaneously every 12 h for 28 days. Study 2: Mothers of preterm infants were randomized to receive r-hPRL (60 μg/kg), placebo or r-hPRL alternating with placebo every 12 h for 7 days.

Measurements: Change in milk volume.

Results: Study 1: Peak prolactin (27·9 ± 17·3 to 194·6 ± 19·5 μg/l; P < 0·003) and milk volume (3·4 ± 1·6 to 66·1 ± 8·3 ml/day; P < 0·001) increased with r-hPRL administration. Study 2: Peak prolactin increased in mothers treated with r-hPRL every 12 h (n = 3; 79·3 ± 55·4 to 271·3 ± 36·7 μg/l; P < 0·05) and daily (101·4 ± 61·5 vs 178·9 ± 45·9 μg/l; P < 0·04), but milk volume increased only in the group treated with r-hPRL every 12 h (53·5 ± 48·5 to 235·0 ± 135·7 ml/day; P < 0·02).

Conclusion: Twice daily r-hPRL increases milk volume in mothers with prolactin deficiency and in preterm mothers with lactation insufficiency.

Fig. 1

Serum prolactin levels in prolactin-deficient mothers (Study 1) before [pre-Tx (Tx = treatment); Subject 1A–5A], during (r-hPRL Tx; Subject 1A–5A) and after treatment (post-Tx; 1B–5B) with recombinant human prolactin (r-hPRL). Time −180 to 0 indicates endogenous serum prolactin levels in individual mothers during a pumping episode before r-hPRL treatment on day 1 (closed circles; pre-Tx; Subject 1A–5A). Serum prolactin levels are depicted starting at time 0 on day 1 (closed circles), day 7 (open circles) and day 28 (cross in circle), with r-hPRL administered at time 0 (r-hPRL Tx; Subject 1A–5A). Endogenous prolactin levels during a pumping episode 1 week after the last dose of r-hPRL are depicted in the second panel for each subject (closed squares; post-Tx; 1B–5B). Breast pumping began at time = 0 and lasted 15 min, as indicated (black rectangles).

Fig. 2

Individual milk volumes over 24 h (Subjects 2–5) in prolactin-deficient mothers during recombinant human prolactin (r-hPRL) treatment (Study 1). Subject 1, the mother with isolated prolactin deficiency, measured breast milk volume only from the first morning pumping episode. The change in milk volume was significant for all subjects (P < 0·001).

Fig. 3

Individual prolactin levels pretreatment [day 1; pre-Tx (Tx = treatment); A1–C1] and post-treatment (day 16; post-Tx; A3–C3) and average prolactin levels during treatment on day 2 (closed circles) and day 8 (closed squares) in the three groups in Study 2 (A2 r-hPRL/r-hPRL; B2 r-hPRL/placebo; C2 Placebo/Placebo). (A) Recombinant human prolactin (r-hPRL) administered every 12 h resulted in an increase in baseline prolactin levels on day 8 (A2) compared to days 1(A1) and 2 (A2) (P < 0·05). R-hPRL every 12 h also increased peak prolactin levels on days 2 and 8 (A2) compared to day 1 (A1) (P < 0·03). (B) R-hPRL alternating with placebo resulted in increased peak prolactin levels on days 2 and 8 (B2) compared to day 1(B1) (P < 0·04). (C) Placebo treatment every 12 h demonstrated no change in baseline or peak prolactin levels (C2) compared to day 1 (C1). However, prolactin levels did increase on day 16 (C3) compared to day 1(C1) in the group treated with placebo (P = 0·02). Black rectangles indicate breast pumping.

Fig. 4

Milk volume in r-hPRL and placebo (Plc) groups (Study 2). (A) Milk volume increased in the group treated with r-hPRL every 12 h (A2 r-hPRL/r-hPRL vs A1). (B) Milk volume did not increase in the group treated with r-hPRL alternating with placebo every 12 h (B2 r-hPRL/Plc vs B1). (C) Milk volume did not increase in the group treated with placebo every 12 h (C2 Plc/Plc vs C1). Subjects with no milk production at baseline are depicted separately from subjects with milk production at baseline. ^★Significantly different from baseline (day 2), P < 0·05.